Virus World

And what that tells us about the pandemic. Like any virus, SARS-CoV-2 has been mutating constantly since the beginning of the pandemic. Until November 2020, though, that didn’t seem to matter. That’s when scientists in the United Kingdom noticed an alarming change: The virus had mutated in a way that made it more transmissible. Within a month, similar reports were emerging from places around the world. Suddenly, it seemed the virus was changing at an alarming rate. SARS-CoV-2 hasn’t actually been mutating faster, though. Instead, by letting it spread around the world, we’ve just given it more and more opportunities to mutate as it replicates. The result is that after countless random mutations, there are signs that the virus is beginning to adapt to our natural defenses. And because it’s completely normal for a virus to change over time, we shouldn’t expect it to stop. The only real way to stop those changes is to stop giving the virus so many opportunities.

Click on this direct link to watch the video:

https://youtu.be/Ha6yUxze1vk 

HANOI, Vietnam (AP) — Vietnam has discovered a new coronavirus variant that’s a hybrid of strains first found in India and the U.K., the Vietnamese health minister said Saturday. Nguyen Thanh Long said scientists examined the genetic makeup of the virus that had infected some recent patients, and found the new version of the virus.  Viruses often develop small genetic changes as they reproduce, and new variants of the coronavirus have been seen almost since it was first detected in China in late 2019. The World Health Organization has listed four global “variants of concern” – the two first found in the U.K. and India, plus ones identified in South Africa and Brazil. Long says the new variant could be responsible for a recent surge in Vietnam, which has spread to 30 of the country’s 63 municipalities and provinces. 

Vietnam was initially a standout success in battling the virus — in early May, it had recorded just over 3,100 confirmed cases and 35 deaths since the start of the pandemic. But in the last few weeks, Vietnam has confirmed more than 3,500 new cases and 12 deaths, increasing the country’s total death toll to 47. Most of the new transmissions were found in Bac Ninh and Bac Giang, two provinces dense with industrial zones where hundreds of thousands of people work for major companies including Samsung, Canon and Luxshare, a partner in assembling Apple products. Despite strict health regulations, a company in Bac Giang discovered that one fifth of its 4,800 workers had tested positive for the virus. In Ho Chi Minh City, the country’s largest metropolis and home to 9 million, at least 85 people have tested positive as part of a cluster at a Protestant church, the Health Ministry said. Worshippers sang and chanted while sitting close together without wearing proper masks or taking other precautions. Vietnam has since ordered a nationwide ban on all religious events. In major cities, authorities have banned large gatherings, closed public parks and non-essential business including in-person restaurants, bars, clubs and spas. Vietnam so far has vaccinated 1 million people with AstraZeneca shots. Last week, it sealed a deal with Pfizer for 30 million doses, which are scheduled to be delivered in the third and fourth quarters of this year. It is also in talks with Moderna that would give it enough shots to fully vaccine 80% of its 96 million people.

State health officials said the California variant is present in about 75% of the island’s cases. 

The NIH on Wednesday announced the start of a phase 1 clinical trial evaluating Moderna’s variant-specific COVID-19 vaccine, saying the shot has been administered to trial participants. Moderna shipped doses of the vaccine — a modified version of its mRNA-1273 vaccine, which has been authorized for use in the U.S. since December — to the NIH last month for testing. The vaccine was tweaked to target the B.1.351 variant, which was first identified in South Africa.  According to the NIH, the new trial will enroll 210 healthy adults at four clinical research sites in Atlanta, Cincinnati, Nashville and Seattle. Investigators at the four sites anticipate that the trial will be fully enrolled by the end of April, the NIH said. The modified vaccine will be studied in both vaccinated and unvaccinated adults. The vaccinated adults already received mRNA-1273 last year as part of a clinical trial. They will be randomly assigned to receive either a single booster vaccination of 50 µg of the modified vaccine, mRNA-1273.351, or a single vaccination containing one 25 µg dose of mRNA-1273 and one 25 µg dose of mRNA-1273.351. A separate clinical trial will assess a booster shot of the original vaccine in the remaining vaccinated study participants. According to National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, the B.1.351 variant has been detected in at least nine U.S. states. The NIAID, which co-developed the vaccine with Moderna, is leading and funding the new trial. “Preliminary data show that the COVID-19 vaccines currently available in the United States should provide an adequate degree of protection against SARS-CoV-2 variants,” Fauci said in the NIH release. “However, out of an abundance of caution, NIAID has continued its partnership with Moderna to evaluate this variant vaccine candidate should there be a need for an updated vaccine.”

NIH Press Release (March 31, 2021):

https://www.nih.gov/news-events/news-releases/nih-clinical-trial-evaluating-moderna-covid-19-variant-vaccine-begins 

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

Posted in bioRxiv (March 21, 2021):

 https://doi.org/10.1101/2021.03.20.436257 

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use.

Methods In this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 micrograms recombinant spike protein with 50 micrograms Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy greater than or equal to 7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants.

Results A total of 4387 participants were randomized and dosed at least once, 2199 with NVX CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 cases in NVX CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: -0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX CoV2373; serious adverse events were rare in both groups.

Conclusions The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection with the presumptive original SARS CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)

Preprint available in medRxiv (March 3, 2021):

https://doi.org/10.1101/2021.02.25.21252477 

The first detailed studies of the so-called P.1 variant show how it devastated a Brazilian city. Now scientists want to know what it will do elsewhere.  In just a matter of weeks, two variants of the coronavirus have become so familiar that you can hear their inscrutable alphanumeric names regularly uttered on television news. B.1.1.7, first identified in Britain, has demonstrated the power to spread far and fast. In South Africa, a mutant called B.1.351 can dodge human antibodies, blunting the effectiveness of some vaccines. Scientists have also had their eye on a third concerning variant that arose in Brazil, called P.1. Research had been slower on P.1 since its discovery in late December, leaving scientists unsure of just how much to worry about it. “I’ve been holding my breath,” said Bronwyn MacInnis, an epidemiologist at the Broad Institute. Now three studies offer a sobering history of P.1’s meteoric rise in the Amazonian city of Manaus. It most likely arose there in November and then fueled a record-breaking spike of coronavirus cases. It came to dominate the city partly because of an increased contagiousness, the research found.  But it also gained the ability to infect some people who had immunity from previous bouts of Covid-19. And laboratory experiments suggest that P.1 could weaken the protective effect of a Chinese vaccine now in use in Brazil.  The new studies have yet to be published in scientific journals. Their authors caution that findings on cells in laboratories do not always translate to the real world, and they’ve only begun to understand P.1’s behavior. “The findings apply to Manaus, but I don’t know if they apply to other places,” said Nuno Faria, a virologist at Imperial College London who helped lead much of the new research.

A new strain of the pandemic coronavirus, first identified and now spreading in California, appears to be somewhat more transmissible and heighten patients’ risk of admission to the intensive care unit (ICU) and death, according to a preprint reporting lab studies and epidemiological data. The variant is also present in other states, but its prevalence among more than 2000 samples collected in California swelled from 0% to greater than 50% between September 2020 and late January, according to researchers at the University of California, San Francisco (UCSF). “This variant is concerning because our data shows that it is more contagious, more likely to be associated with severe illness, and at least partially resistant to neutralizing antibodies,” says senior author Charles Chiu, an infectious diseases physician and sequencing expert at UCSF. The data suggest the new strain “should likely be designated a variant of concern warranting urgent follow-up investigation,” the authors write in their preprint, which has not been peer reviewed and which they say is expected to be posted online soon.  The findings “warrant taking a much closer look at this variant,” says Angela Rasmussen, a virologist at Georgetown University’s Center for Global Health Science and Security who was not involved with the research. They “underscore the importance of pulling out all the stops in terms of both exposure reduction and increased vaccine distribution and access.” But other coronavirus experts say more data are needed before conclusions are drawn, noting that among patients with the variant, the study included fewer than 10 who were admitted to the ICU and fewer than 10 who died. “If I were a reviewer, I would want to see more data from more infected people to substantiate this very provocative claim,” says David O’Connor, a viral sequencing expert at the University of Wisconsin, Madison, who was not part of the research.

For their study, the authors sequenced 2172 genomes from virus samples captured from patients in 44 California counties between 1 September 2020 and 29 January. The new variant, which comes in two forms labeled B.1.427 and B.1.429 that carry slightly differing mutations, accounted for 21.3% of these sequences overall. (Under a different naming scheme, the variant is sometimes referred to as 20C/L452R.) The scientists also studied the medical records of 324 people with COVID-19 who were cared for at UCSF clinics or its medical center. The researchers adjusted the data to account for differences in age, gender, and ethnicity, and found that, compared with patients who had other viral strains, those carrying the variant were 4.8 times more likely to be admitted to the ICU and more than 11 times more likely to die. Other data suggest the variant is more contagious. The scientists found that people infected with the variant harbored about twice as much virus in their noses, an index of viral shedding, which may make them more infectious to others. In the lab, viruses engineered to carry a key mutation found in the variant were better than control viruses at infecting human cells and lunglike structures called organoids. And in one nursing home where the variant took hold, it spread severalfold faster than in four other nursing home outbreaks caused by other viral variants. “The evidence is growing that this [variant] is more transmissible than [its] immediate competitors,” although not as transmissible as some other variants of concern, says William Hanage, an expert on viral evolution at the Harvard T.H. Chan School of Public Health. (Variants of concern are coronaviruses with mutations that make them more likely to spread, evade vaccines, or make people sicker.) In lab studies, B.1.429 also impacted the effectiveness of antibodies: It was four times less susceptible than the original coronavirus to neutralizing antibodies from the blood of people who recovered from COVID-19, and two times less susceptible to antibodies from the blood of people vaccinated with the Pfizer or Moderna vaccines. That diminished potency is “moderate but significant,” the researchers wrote. Robert Schooley, an infectious disease physician and virologist at UC San Diego, praised the paper’s ambition and noted its findings of high viral loads in infected people’s noses. “The biology of having a higher level of virus … would certainly fit the thesis that people would not do as well,” he says. That comports with the fact that “we are seeing here in Southern California more people … for a longer period of time in our ICUs.” The patient data suggest the variants may be linked to worse outcomes. But although the ICU and mortality findings reached statistical significance, the numbers were small: Eight of 61, or 13%, of hospitalized patients with the variants were admitted to the ICU, compared with seven of 244, or 2.9%, of hospitalized patients who did not harbor the variants. Seven of 62 people (or 11.3%) with the variants died, versus five of 246 (or 2%) of people without the variants. The authors admit it is not possible to tell whether the variants actually make people sicker or whether, for instance, most of the patients with the variant got sick during the worst months of the pandemic, when health care systems were overloaded and patient care may have been suboptimal. All the variant-infected patients in the study who died at UCSF did so between 22 December 2020 and 28 January, when the area was experiencing a surge of infections. “Could any of the seven individuals who died with this variant have survived if they received treatment when the state wasn’t in the midst of a surge?” O’Connor asks. “It’s really impossible to know, as the authors acknowledge.”

In addition to other mutations, B.1.427 and B.1.429 each have an identical trio of mutations in the coronavirus spike protein, which allows the virus to invade human cells. One of those mutations, dubbed L452R, is thought to stabilize the interaction between the spike protein and the receptor it uses to attach to and invade human cells, increasing infectivity. None of those three spike mutations is found in the three other variants of concern, which emerged in the United Kingdom, South Africa, and Brazil. Evolutionary biologists also caution against overinterpreting the study. “The work is definitely worth reporting, but I don’t buy that on its own this is sufficient to categorize these as variants of concern,” Hanage says. He notes that B.1.427 and B.1.429 likely emerged in July and June 2020, respectively, but infections have not exploded in the exponential curves seen with the three identified variants of concern. “The real evidence will be seeing if, when introduced elsewhere, these lineages start to take off in similar fashion.” The paper also offers another cautionary tale about the United States’s subpar effort to sequence coronavirus samples nationwide. It’s “worrisome” that a state like Nevada, which borders California, has fewer than 500 sequences in GISAID, the leading coronavirus sequence repository, O’Connor says. The limited data from Nevada currently suggest the variant represents 27% of collected sequences, according to a database created by Scripps Research using GISAID data. 

Doctors in France are treating a critically ill patient infected with the South African coronavirus variant, four months after he recovered from COVID-19, in what study authors said was the first case of its kind.  The 58-year-old man had a history of asthma and initially tested positive for COVID-19 in September when he presented to medical staff with a fever and shortness of breath. The symptoms persisted only for a few days, and the man tested negative for COVID-19 twice in December 2020. However, he was admitted to hospital in January and diagnosed with the South African variant. The patient's condition worsened, and he is currently in a "critical condition" on a ventilator. 

"This is, to our knowledge, the first description of reinfection with the South African (variant) causing severe COVID-19, four months after a first mild infection," said authors of a study published this week in the journal Clinical Infectious Diseases. The 501Y.V2 coronavirus variant emerged late last year in South Africa and immediately provoked alarm among disease specialists. It has eight key mutations, one of which affects the virus' spike protein, making it more effective at binding to human cells and therefore more infectious. Vaccine manufacturers Pfizer/BioNTech and Moderna say their mRNA vaccines retain their effectiveness against the South African variants and another that emerged last year in Britain. However a study last week showed that AstraZeneca's vaccine failed to prevent mild and moderate cases of infection of the South African variant. "The impact of 501Y.V2 mutations on the effectiveness of vaccines developed based on earlier SARS-CoV-2 strains is still unknown," said the authors of the reinfection study.

Case study published in Clinical Infectious Diseases (Feb. 10, 2021):

https://doi.org/10.1093/cid/ciab129

SARS-CoV-2 has been mutating since it was first sequenced in early January 2020. Here, we analyze 45,494 complete SARS-CoV-2 geneome sequences in the world to understand their mutations. Among them, 12,754 sequences are from the United States. Our analysis suggests the presence of four substrains and eleven top mutations in the United States. These eleven top mutations belong to 3 disconnected groups. The first and second groups consisting of 5 and 8 concurrent mutations are prevailing, while the other group with three concurrent mutations gradually fades out. Moreover, we reveal that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. One of the top mutations, 27964C > T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we uncover that two of four SASR-CoV-2 substrains in the United States become potentially more infectious. Rui Wang et al. report a comprehensive analysis of nearly 13,000 SARS-CoV-2 genome sequences isolated from patients in the United States, comprising more than 7000 single mutations. They show that SARS-CoV-2 genomes cluster into four distinct groups and that two of these groups are potentially more infectious, underlining the urgent need for viral control strategies in the US.

Findings Published in Communications Biology (Feb. 15, 2021):

https://www.nature.com/articles/s42003-021-01754-6

medRxiv - The PrexThe new SARS-CoV-2 variant B.1.1.7 was identified in December 2020 in the South-East of England, and rapidly increased in frequency and geographic spread. While there is some evidence for increased transmissibility of this variant, it is not known if the new variant presents with variation in symptoms or disease course, or if previously infected individuals may become reinfected with the new variant. Using longitudinal symptom and test reports of 36,920 users of the Covid Symptom Study app testing positive for COVID-19 between 28 September and 27 December 2020, we examined the association between the regional proportion of B.1.1.7 and reported symptoms, disease course, rates of reinfection, and transmissibility. We found no evidence for changes in reported symptoms, disease severity and disease duration associated with B.1.1.7. We found a likely reinfection rate of around 0.7% (95% CI 0.6-0.8), but no evidence that this was higher compared to older strains. We found an increase in R(t) by a factor of 1.35 (95% CI 1.02-1.69). Despite this, we found that regional and national lockdowns have reduced R(t) below 1 in regions with very high proportions of B.1.1.7.

Available in medRxiv (Jan. 29, 2021):

 https://doi.org/10.1101/2021.01.28.21250680 

Health authorities identified the first U.S. cases of a fast-spreading form of the coronavirus initially seen in South Africa.  Neither person has a history of travel to countries where the variant has been confirmed, and there is no connection between the two people, South Carolina health officials said Thursday. That indicates there has been some local spread of the variant after it arrived in the United States. One case was found in South Carolina’s Pee Dee region, and one in the Lowcountry.  The announcement Thursday means that three coronavirus variants that appear to be more contagious and have emerged in recent months have all been documented in the United States. But in a way, the news was no surprise to experts. They had for weeks said the variant that first cropped up in South Africa, called B.1.351, was likely already in the U.S., but this country’s limited system of surveillance for different iterations of the coronavirus meant the variant likely went unnoticed once it was imported via a traveler and could have even been spreading. Earlier this week, Minnesota health officials confirmed the first Covid-19 case caused by P.1, a variant first identified in Brazil. There have been a few hundred U.S. cases of the B.1.1.7 variant, which initially appeared in the United Kingdom. All three variants are thought to be more transmissible than earlier forms of the coronavirus and, if left unchecked, could lead to more cases overall by infecting more people faster. The Centers for Disease Control and Prevention has estimated that B.1.1.7 could become the dominant form of the coronavirus in the United States by March.

“It’s critical that we all continue to do our part by taking small actions that make a big difference,” Brannon Traxler, South Carolina’s interim public health director, said in a statement. “These include wearing our masks, staying at least six feet apart from others, avoiding large crowds, washing our hands, getting tested often, and when we can, getting vaccinated. These are the best tools for preventing the spread of the virus, no matter the strain.” The three variants evolved independently — all viruses mutate and occasionally pick up alterations that give them a transmission advantage — but happen to share some of the same mutations.  B.1.351 and P.1 in particular have raised a different set of alarms than B.1.1.7. Studies have shown that mutations that appear in both variants can help the virus partially evade the human immune response, perhaps making it more likely the variants could reinfect people who had an initial case of Covid-19. Such studies resulted in concerns that existing Covid-19 vaccines — which were designed based on earlier iterations of the virus — might not be as effective against the variants. On Thursday, for example, Novavax said its experimental Covid-19 vaccine was 90% effective in one trial in the U.K., but that in a separate trial in South Africa, it was 49% effective. Of the cases that occurred in the South Africa trial for which there was sequencing data, 93% were caused by B.1.351. Other vaccines made in different ways may see less of a drop in efficacy, though more studies are ongoing. With the mRNA vaccines from Pfizer-BioNTech and Moderna, it seems like the shots do lose some of their neutralizing potency against some of the mutations seen in both P.1 and B.1.351, but that the immune response elicited by the vaccines is so overwhelmingly powerful that the shots can withstand a loss of some of their oomph while still protecting people from getting sick with Covid-19.

On Monday, Moderna said its shot should still be effective against B.1.351 despite the fact that the neutralizing antibodies generated by the vaccine do not recognize the form of the virus as well as other forms. Essentially, the antibody response induced by the shot should still be sufficient to help people ward off Covid-19. There is a question, however, of whether the immune response from the vaccines will last as long against the variants as earlier viral iterations. So far, the studies investigating the impact of variants on the Pfizer and Moderna vaccines have largely focused on neutralizing antibodies, but experts note the shots also rally other parts of the immune system — including T cells, B cells, and other types of antibodies — providing additional reasons that the current vaccines should still broadly work against the variants.  Still, experts do think the coronavirus could one day pick up a certain suite of mutations that does threaten the shots’ overall effectiveness, so, they say, vaccine makers and regulators should start considering what will be required to update the immunizations to better match circulating forms of SARS-CoV-2, the scientific name of the coronavirus causes Covid-19.

Moderna and Novavax have said they are studying booster shots designed specifically against B.1.351. For now, the most pressing concern about the variants, experts stress, remains their infectiousness. The World Health Organization, for example, warned on Thursday that B.1.351 was driving a surge in cases as it spread out of South Africa into other African nations, with Matshidiso Moeti, the WHO’s regional director, saying the continent “is at a crossroads.” Cases in the United States remain sky-high, but they are coming down from peaks earlier this month. If any of the variants take off, the country could see yet another spike. It will also take a greater portion of the population to be immune to the virus to slow the spread of more contagious variants, adding even more pressure to the U.S. vaccine campaign.  In the past week, scientists in the U.K. have been reporting that the variant first seen there, B.1.1.7, may also be deadlier than other forms of the virus, though they are still parsing through national data. Generally, experts actually fear a more transmissible virus more than one that is correspondingly more lethal; more infectious variants could lead to more deaths overall even if they’re not deadlier just because they result in that many more cases. But with B.1.1.7, “unfortunately, it looks as if this virus might be both,” said John Edmunds of the London School of Hygiene & Tropical Medicine.

A coronavirus variant known as "lambda" is gaining the attention of health officials as it spreads around the world. The variant, also known as C.37, was first detected in Peru in August 2020, according to the World Health Organization (WHO). On June 14, the agency designated C.37 a global "variant of interest," or VOI, and named it lambda. VOI means the variant is increasingly showing up in communities and has mutations that are predicted to have some effect on viral characteristics, such as increased transmissibility. In contrast, officials use the term "variant of concern," or VOC, once reliable data shows that the variant has increased transmissibility — such as what's been seen with the delta variant — or other worrying features. So far, lambda has been detected in 29 countries, with high levels of spread in South American countries. In recent months, the lambda variant was detected in 81% of COVID-19 cases in Peru that underwent genetic sequencing, according to the WHO. And in Chile, the variant was detected in about one-third of cases, the WHO said. 

Most recently, the variant popped up in the United Kingdom. On June 25, Public Health England reported six cases of the lambda variant, all of which were tied to overseas travel. Officials are monitoring the lambda variant because it carries a number of mutations that could potentially aid its spread. The variant has seven mutations in the virus's "spike protein" compared with the original strain of SARS-CoV-2 detected in Wuhan, China. Some of these mutations have the potential to increase transmissibility of the virus or to reduce the ability of certain antibodies to neutralize, or inactivate, the virus, according to the WHO. For example, lambda has a mutation known as F490S located in the spike protein's receptor-binding domain (RBD), where the virus first docks onto human cells. A paper published in the July issue of the journal Genomics identified F490S as a likely "vaccine escape mutation" that could both make the virus more infectious and disrupt the ability of vaccine-generated antibodies to recognize the variant.  Still, these effects are theoretical at this point. "There is currently no evidence that this variant causes more severe disease or renders the vaccines currently deployed any less effective," according to Public Health England. More studies are needed to see if these mutations really do affect how the virus behaves.

GAITHERSBURG, Md., June 11, 2021 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX), a biotechnology company developing next-generation vaccines for serious infectious diseases, today announced preclinical and clinical data on the company's original recombinant protein COVID-19 vaccine candidate, NVX-CoV2373, and for a new vaccine directed against the SARS-CoV-2 Beta (B.1.351) variant, which was originally identified in South Africa. The data show that the vaccines demonstrated strong immunogenicity and protection against both the Alpha (B.1.1.7) variant, which was originally identified in the United Kingdom, and the Beta (B.1.351) variant as well as the original SARS-CoV-2 in animal and human studies. A preprint of the manuscript, 'Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants,' is available at bioRxiv.org and has been submitted for peer review. "While current vaccines are effective against selected SARS-CoV-2 variant strains, newly emerging variants are also being identified that have the ability to overcome vaccine induced immunity," said Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine, who collaborated on these studies. "This work demonstrates that variant vaccines that protect against these newly emerging variants have the potential to be highly effective and may produce broader protection against variants we know of and those that will arise in the future. Clinical trials will provide further evidence on the effectiveness of variant vaccines."  The studies compared the Beta (B.1.351)-directed vaccine to Novavax' prototype vaccine candidate as standalone, in combination, and as heterologous prime boost vaccine. The findings show a broad array of cellular and humoral responses in animal models against all virus strains evaluated. The Alpha (B.1.1.7) and Beta (B.1.351) variant strains have created public health concerns due to increased transmission rates and lower efficacy of current vaccines seen against Beta (B.1.351). "These data suggest that not only could one booster dose of this variant-directed vaccine potentially provide a robust, protective immune boost after vaccination against the original SARS-CoV-2 virus, but also the potential to provide broad protection against various virus strains if used as a primary vaccine regimen," said Gregory M. Glenn, M.D., President of Research and Development, Novavax. "This broad immune coverage is vital to controlling the pandemic as variants of concern continue to emerge worldwide that could jeopardize the protection created through ongoing COVID-19 vaccination efforts."

Study 1: Immunogenicity and Protection in Mice

Mice were immunized with NVX-CoV2373 or rS-B.1.351 alone, in combination, or as a heterologous prime boost. Mice vaccinated with any of the four regimens displayed elevated antibody titers against both the original and Beta (B.1.351) spike. Heterologous or bivalent vaccination is highly immunogenic against the prototype spike compared to monovalent approaches, while immunization with monovalent rS-B.1.351 or bivalent spike resulted in the highest anti-B.1.351 spike IgG titers among regimens tested.

Additionally, mice immunized with rS-B.1.351 alone produced elevated neutralizing antibody titers to the Alpha (B.1.1.7) and Beta (B.1.351) strains compared to titers upon immunization with the prototype-directed strain. Titers were similar in the heterologous and bivalent vaccine groups. Antibodies produced after vaccination with rS-B.1.351 inhibited binding between human angiotensin converting enzyme-2 receptor (hACE2) and the variant spike or original spike to the same degree. This indicates that rS-B.1.351 can efficiently protect "backward" against original SARS-CoV-2 strains. In contrast, NVX-CoV2373 was less efficient at protecting "forward" against the Beta (B.1.351) variant strain. Whether immunized with prototype vaccine or rS-B.1.351 alone, in combination, or as a heterologous prime boost, mice were protected when challenged with live Alpha (B.1.1.7) or Beta (B.1.351) variant strains of SARS-CoV-2.

Study 2: Anamnestic Response in Baboons

A cohort of baboons that were originally immunized with prototype vaccine were boosted approximately one year later with one or two doses of rS-B.1.351. Seven days after the first rS-B.1.351 boost, those that originally received adjuvanted prototype-directed vaccine exhibited a strong immune response, with anti-Spike IgG titers that were higher than the peak immune response observed during the primary immunization series. The rS-B.1.351 boost elicited comparable antibody titers against original and rS-B.1.351 spike. Further, the same cohort exhibited a strong neutralizing response to Alpha (B.1.1.7) and Beta (B.1.351) strains and hACE2-inhibiting antibody response following the boost, despite having undetectable titers before the boost. High neutralizing antibody titers were observed seven days post-boost, demonstrating "a robust, durable antibody response even one year after the primary vaccination series." These results suggest that one dose of a variant-directed vaccine may be sufficient for boosting regimens after previous immunization with a COVID-19 vaccine based on the original spike strain.

Study 3: Robust Antibody Response in Humans

NVX-CoV2373 is currently being studied in multiple clinical trials, including in locations where Alpha (B.1.1.7) and Beta (B.1.351) variant strains are widespread. Thirty randomly selected human serum samples from Phase 2 clinical trial participants after their second dose of the vaccine were assayed. The sera were analyzed for their ability to neutralize Alpha (B.1.1.7) and Beta (B.1.351) strains. The trial participants' sera demonstrated a neutralizing capacity of the Alpha (B.1.1.7) strain equal to NVX-CoV2373, with a modest reduction in neutralizing capacity against the Beta (B.1.351) strain. These data support the development and production of a Beta (B.1.351) targeted vaccine, which also demonstrated to be efficient at protecting mice against Beta (B.1.351) and to induce a strong response in primates originally immunized with NVX-CoV2373. Furthermore, the data support that a booster vaccine containing a variant strain could both increase antibody levels as well as broaden coverage. Novavax expects to initiate further clinical testing of rS-B.1.351 in the fall of 2021....

See bioRxiv (June 9, 2021):

https://doi.org/10.1101/2021.06.08.447631 

Brazil's P1 coronavirus variant, behind a deadly COVID-19 surge in the Latin American country that has raised international alarm, is mutating in ways that could make it better able to evade antibodies, according to scientists studying the virus.  Research conducted by the public health institute Fiocruz into the variants circulating in Brazil found mutations in the spike region of the virus that is used to enter and infect cells. Those changes, the scientists said, could make the virus more resistant to vaccines - which target the spike protein - with potentially grave implications for the severity of the outbreak in Latin America’s most populous nation. “We believe it’s another escape mechanism the virus is creating to evade the response of antibodies,” said Felipe Naveca, one of the authors of the study and part of Fiocruz in the Amazon city of Manaus, where the P1 variant is believed to have originated. Naveca said the changes appeared to be similar to the mutations seen in the even more aggressive South African variant, against which studies have shown some vaccines have substantially reduced efficacy.

“This is particularly worrying because the virus is continuing to accelerate in its evolution,” he added. Studies have shown the P1 variant to be as much as 2.5 times more contagious than the original coronavirus and more resistant to antibodies. On Tuesday, France suspended all flights to and from Brazil in a bid to prevent the variant’s spread as Latin America’s largest economy becomes increasingly isolated. The variant, which has quickly become dominant in Brazil, is thought to be a large factor behind a massive second wave that has brought the country’s death toll to over 350,000 - the second highest in the world behind the United States.  Brazil’s outbreak is also increasingly affecting younger people, with hospital data showing that in March more than half of all patients in intensive care were aged 40 or younger. For Ester Sabino, a scientist at the faculty of medicine of the University of Sao Paulo who led the first genome sequencing of the coronavirus in Brazil, the mutations of the P1 variant are not surprising given the fast pace of transmission. “If you have a high level of transmission, like you have in Brazil at the moment, your risk of new mutations and variants increases,” she said. Fiocruz researchers including Naveca also recently described a novel variant descended from a different lineage to P1, and detected in the northeast of the country, that carried 14 defining mutations including the E484K change first noted in the South African variant (bit.ly/2RBhLKD).

SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD) as the two main targets of neutralizing antibodies (Abs). A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California and is currently spreading throughout the US and 29 additional countries. It is unclear whether antibody responses to SARS-CoV-2 infection or to the prototypic Wuhan-1 isolate-based vaccines will be impacted by the three B.1.427/B.1.429 S mutations: S13I, W152C and L452R. Here, we assessed neutralizing Ab responses following natural infection or mRNA vaccination using pseudoviruses expressing the wildtype or the B.1.427/B.1.429 S protein. Plasma from vaccinated or convalescent individuals exhibited neutralizing titers, which were reduced 3-6 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The RBD L452R mutation reduced or abolished neutralizing activity of 14 out of 35 RBD-specific monoclonal antibodies (mAbs), including three clinical-stage mAbs. Furthermore, we observed a complete loss of B.1.427/B.1.429 neutralization for a panel of mAbs targeting the N-terminal domain due to a large structural rearrangement of the NTD antigenic supersite involving an S13I-mediated shift of the signal peptide cleavage site. These data warrant closer monitoring of signal peptide variants and their involvement in immune evasion and show that Abs directed to the NTD impose a selection pressure driving SARS-CoV-2 viral evolution through conventional and unconventional escape mechanisms.

Preprint available at bioRxiv (April 1, 2021):

https://doi.org/10.1101/2021.03.31.437925 

Antibodies from people infected with the 501Y.V2 coronavirus variant first identified in South Africa are also effective against previously circulating variants, suggesting that vaccines against 501Y.V2 might work against a range of coronavirus variants. South Africa’s first wave of coronavirus infections peaked in July 2020. The second wave peaked in January 2021, and was driven by the recently discovered 501Y.V2 variant (also called B.1.351). The variant is partially resistant to antibodies against previously circulating variants, raising concerns about the effectiveness of current vaccines against it. Tulio de Oliveira at the University of KwaZulu-Natal in Durban, South Africa, Alex Sigal at the Africa Health Research Institute, also in Durban, and their colleagues tested blood plasma from people in South Africa who had been infected during one of the two waves (S. Cele et al. Nature https://doi.org/f362; 2021). The team found that plasma from the second wave was 15 times more effective at preventing the 501Y.V2 variant from infecting cells in a laboratory dish, compared with plasma from the first wave. The scientists also found that second-wave plasma could neutralize first-wave variants with an effectiveness similar to that of the Pfizer–BioNTech vaccine. This implies that updated vaccines against 501Y.V2 could also protect against earlier coronavirus variants.

Original Findings Published in Nature (March 29, 2021):

https://doi.org/10.1038/s41586-021-03471-w 

Concern about new coronavirus variants has grown quickly in recent months. First, scientists in the United Kingdom spotted a more contagious coronavirus strain that spread like wildfire through the London area. Then, researchers in South Africa spotted one that appears to evade the immune system. Next, another variant was flagged in Brazil because it looked like it could infect people who had already been infected once before. And now there has been a flurry of reports about homegrown variants in the United States. What's going on? How worried do we really need to be about them? The short answer is, worried but probably not panicked. The virus is doing what viruses do: evolving to find new ways to continue to infect people. "It's infected millions of humans around the world now, and it's probably just getting into a more intimate relationship with our species," says Jeremy Kamil of Louisiana State University, who spotted a mutation that the virus appears to have evolved repeatedly in different parts of the United States.  The fear is that just as humanity appears to be finally turning the corner in the battle against the virus, the variants could give the pathogen the upper hand once again. They could trigger a new surge. And new, even more worrisome variants could emerge because the virus is still spreading so widely. "They're definitely something that we need to be paying attention to and designing our pandemic response around," says Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle. "I don't think the sky is falling, but I think it's something that absolutely bears attention."

Viruses mutate all the time. Most of the time, those mutations don't pose a threat. But the current crop of coronavirus mutations has made the virus more contagious and may have made the virus more likely to make people seriously sick. It appears the mutations may also make it more likely people could get reinfected and make the vaccines less effective. But we're fighting back: The vaccines are rolling out, and so far it looks like they work against the variants to protect people from getting very sick or dying. If enough people in the U.S. can get vaccinated fast enough while also keeping up safe behaviors, this could prevent another major surge of cases and deaths. It could also help prevent new, dangerous variants from evolving because the more the virus spreads, the greater chance it has to mutate.  Here's a primer on the variants that scientists are watching most closely:

Variant B.1.1.7: first spotted in the U.K.

This variant is still the strain that public health experts in the U.S. are most concerned about. That's because it clearly is far more contagious than the original strain — perhaps 50% more infectious. This variant also looks like it may make people sicker. And it appears to be already fairly widespread in the United States. At least 2,500 cases have been confirmed in at least 46 states, according to the Centers for Disease Control and Prevention. Its real prevalence, like that of other variants, is assumed to be far more widespread. The U.S. isn't sequencing the DNA of enough virus samples to know exactly how much more prevalent. But the CDC has predicted it will become the dominant strain throughout the U.S. later this month.

Variant B.1.351: first spotted in South Africa

Scientists are also alarmed by this variant because it evolved a mutation that appears to make it stealthier. That mutation is known as E484K (sometimes pronounced "eek"), and it appears to make the virus better at evading antibodies produced by the immune system. That means some drugs don't work against this variant. It also might be able to infect people who have already recovered from the virus. And, most concerning, laboratory studies suggest the vaccines may be less effective against it. This variant has been confirmed at least 65 times in at least 17 U.S. states, according to the CDC.

Variant P.1: first spotted in Brazil

This strain, frequently called P.1, also has the E484K mutation. It set off alarms because it swept through the Amazonian city of Manaus, which had already been ravaged by the virus. That indicated it could evade the body's natural defenses and reinfect people. It has been spotted at least 10 times in at least five U.S. states so far.

But wait, there's more: emerging U.S. variants

More recently, scientists have started identifying homegrown variants in the U.S. that have raised red flags. Two have gotten the most attention: 1) A variant that has been spreading quickly in California, B.1.427, appears to be more contagious than the original strain but not as contagious as the variant first spotted in the United Kingdom. While researchers at the University of California, San Francisco, reported some evidence that it may make people sicker, that finding remains weak so far. 2) Another variant appears to have started spreading quickly in New York City in January. Called B.1.526, it's concerning because it has that stealthy E484K mutation. While some researchers think it may be more of a concern than the variant spotted in California, it remains unclear whether it is more contagious and how much of a threat it may pose. But it has been spotted elsewhere in the Northeast. "It's something we should keep an eye on and make sure that we continue to monitor the situation," says Kristian Andersen, a scientist at the Scripps Research Institute. But that doesn't mean it will turn out to be a serious problem, he adds.

"There's a lot of things we need to keep eyes on, and then we keep our eyes on it, and then it turns out to not be important. In fact, the vast majority of situations [are] exactly that." But, Andersen adds: "We do have these other variants that we need to keep absolute focus on because we know they are of concern."

The daily toll reached 1,641 on Tuesday, Brazil's highest figure since the pandemic started.  The health ministry said 1,641 people had died with Covid in the previous 24 hours. The record was reached as scientists said that a new variant first found in Brazil appears more contagious. Brazil, where more than a quarter of a million people have died with Covid, has the second highest coronavirus death toll after the United States.

Two separate teams of researchers have found a worrying new coronavirus variant in New York City that carries mutations that help it evade the body's natural immune response -- as well as the effects of monoclonal antibody treatments.  Genomics researchers have named the variant B.1.526. It appears in people affected in diverse neighborhoods of New York City, they said, and is "scattered in the Northeast." One of the mutations in this variant is the same concerning change found in the variant first seen in South Africa and known as B.1.351. It appears to evade, somewhat, the body's response to vaccines, as well. And it's becoming more common. "We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.7% in the past two weeks," one team, at Columbia University Medical Center, write in a report that has yet to be published, although it is scheduled to appear in pre-print version this week.  It's the latest of a growing number of viral variants that have arisen in the US, which has had more coronavirus cases -- 28 million -- than any other country and where spread is still intense. It's "home grown, presumably in New York," Dr. David Ho, Director of the Aaron Diamond AIDS Research Center at Columbia, who led the study team, said by email.  Viruses mutate all the time. The more people who are infected, and the longer they are infected, the more chance the viruses have to change. A patient's body will be loaded with billions of copies of a virus, and may will be slightly changed, or mutated. Most will come and go. But sometimes a mutation or pattern of mutations takes hold and gets passed along. If viruses with such patterns become more common, they're called variants. Again, it's not unusual for variants to arise but if they give the virus worrying properties, such as better transmissibility or the ability to evade treatments and vaccines, that's when doctors start to worry.

Preliminary findings suggest that B.1.1.7, a SARS-CoV-2 variant first identified in the United Kingdom, might be more transmissible because it spends more time inside its host than earlier variants do. Previous studies have estimated that B.1.1.7, which is now spreading rapidly in a number of countries, is roughly 50% more contagious than earlier coronavirus variants are. Yonatan Grad at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and his colleagues examined the results of daily SARS-CoV-2 tests on 65 people infected with SARS-CoV-2, including 7 infected with B.1.1.7 (S. M. Kissler et al. Preprint at https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37366884; 2021).

The team looked at how long the virus persisted, and the amount of virus present at each time point. In people infected with B.1.1.7, infections lasted an average of 13.3 days, compared with 8.2 days in people with other variants. There was little difference in the peak concentrations of the virus between the two groups. These findings hint that B.1.1.7 is more easily transmitted than other variants are because people who catch it are infected for a relatively long time, and can therefore infect a larger number of contacts. This suggests that longer quarantine periods might be warranted for individuals infected with this variant. The findings have not yet been peer reviewed.

Preprint available at:

https://dash.harvard.edu/handle/1/37366884 

A new coronavirus variant with three mutations "of biological significance" has been detected in 11 countries, according to a new academic report. This new variant, B.1.525, has been found on several continents, academics at the University of Edinburgh noted in an assessment of the variant published on Monday.

Here are countries where it has been found:

• United States
• Canada
• Denmark
• United Kingdom
• France
• Belgium
• Spain
• Nigeria
• Ghana
• Jordan
• Australia

The bad news, coming nearly a week after a million doses of the AstraZeneca-Oxford vaccine arrived in South Africa, was a big setback for the country.  South Africa halted use of the AstraZeneca-Oxford coronavirus vaccine on Sunday after evidence emerged that the vaccine did not protect clinical trial volunteers from mild or moderate illness caused by the more contagious virus variant that was first seen there. The findings were a devastating blow to the country’s efforts to combat the pandemic.  Scientists in South Africa said on Sunday that a similar problem held for people who had been infected by earlier versions of the coronavirus: The immunity they acquired naturally did not appear to protect them from mild or moderate cases when they were reinfected by the variant, known as B.1.351. The developments, coming nearly a week after a million doses of the AstraZeneca-Oxford vaccine arrived in South Africa, were an enormous setback for the country, where more than 46,000 people are known to have died from the virus They were also another sign of the dangers posed by new mutations in the coronavirus. The B.1.351 variant has spread to at least 32 countries, including the United States. The number of cases evaluated as part of the studies outlined by South African scientists on Sunday were low, making it difficult to pinpoint just how effective or not the vaccine might be against the variant.  And because the clinical trial participants who were evaluated were relatively young and unlikely to become severely ill, it was impossible for the scientists to determine if the variant interfered with the AstraZeneca-Oxford vaccine’s ability to protect against severe Covid-19, hospitalizations or deaths. The scientists said, however, that they believed the vaccine might protect against more severe cases, based on the immune responses detected in blood samples from people who were given it. If further studies show that to be the case, South African health officials will consider resuming use of the AstraZeneca-Oxford vaccine, they said.

The new research findings have not been published in a scientific journal. But the discovery that the AstraZeneca-Oxford product showed minimal efficacy in preventing mild and moderate cases of the new variant added to the mounting evidence that B.1.351 makes current vaccines less effective. Pfizer and Moderna have both said that preliminary laboratory studies indicate that their vaccines, while still protective, are less effective against B.1.351. Novavax and Johnson & Johnson have also sequenced test samples from their clinical trial participants in South Africa, where B.1.351 caused the vast majority of cases, and both reported lower efficacy there than in the United States.  “These results are very much a reality check,” Shabir Madhi, a virologist at University of the Witwatersrand who ran the AstraZeneca-Oxford vaccine trial in South Africa, said of the findings released on Sunday. The pause in the country’s rollout of the AstraZeneca-Oxford vaccine means that the first shipments will now be put in warehouses. Instead, South African health officials said they would inoculate health workers in the coming weeks with the Johnson & Johnson vaccine, which has shown strong efficacy in preventing severe cases and hospitalizations caused by the new variant. Johnson & Johnson has applied for an emergency use authorization in South Africa. But health officials there indicated that even before it is authorized, some health workers could be given the vaccine as part of an ongoing trial. In the AstraZeneca-Oxford trial in South Africa, roughly 2,000 participants were given either two doses of the vaccine or placebo shots. There was virtually no difference in the numbers of people in the vaccine and placebo groups who were infected with B.1.351, suggesting that the vaccine did little to protect against the new variant. Nineteen of the 748 people in the group that was given the vaccine were infected with the new variant, compared with 20 out of 714 people in the group that was given a placebo.

That equates to a vaccine efficacy of 10 percent, though the scientists did not have enough statistical confidence to know for sure whether that figure would hold among more people. Researchers also conducted laboratory experiments on blood samples from people who had been vaccinated and found a significant reduction in the activity levels of vaccine-generated antibodies against the B.1.351 variant compared with other lineages. Beyond the troubling news about the AstraZeneca-Oxford vaccine, Dr. Madhi reported evidence suggesting that past infection by earlier versions of the coronavirus did not protect people in South Africa from the B.1.351 variant. In order to determine who had previously been infected by the coronavirus, researchers tested blood samples from people who had enrolled in a trial of the Novavax vaccine, but who were given placebo shots and not the vaccine itself.  The researchers compared the levels of infection by the new variant in people who showed evidence of having previously had Covid-19 with the levels of infection in people who did not, and found no difference. That suggested, Dr. Madhi wrote on a slide presented Sunday night, that “past infection by ‘original’ variants of SARS-CoV-2 do NOT protect against mild and moderate Covid-19 from the B.1.351 variant.....”

University of Witwatersrand, Johannesburg (Feb. 7, 2021):

https://www.wits.ac.za/covid19/covid19-news/latest/oxford-covid-19-vaccine-trial-results.html 

An early analysis in Britain found that the vaccine had an efficacy rate of nearly 90 percent. But in a small South Africa trial, the efficacy rate dropped to just under 50 percent. Novavax, a little-known company supported by the U.S. federal government’s Operation Warp Speed, said for the first time on Thursday that its Covid-19 vaccine offered robust protection against the virus. But it also found that the vaccine is not as effective against the fast-spreading variant first discovered in South Africa, another setback in the global race to end a pandemic that has already killed more than 2.1 million people. That could be a problem for the United States, which hours earlier reported its first known cases of the contagious variant in two unrelated people in South Carolina. And it came just days after Moderna and Pfizer said that their vaccines were also less effective against the same variant. Novavax, which makes one of six vaccine candidates supported by Operation Warp Speed last summer, has been running trials in Britain, South Africa, the United States and Mexico. It said Thursday that an early analysis of its 15,000-person trial in Britain revealed that the two-dose vaccine had an efficacy rate of nearly 90 percent there. But in a small trial in South Africa, the efficacy rate dropped to just under 50 percent. Almost all the cases that scientists have analyzed there so far were caused by the variant, known as B.1.351. The data also showed that many trial participants were infected with the variant even after they had already had Covid.

“We have the first trial — we are the first to conduct an efficacy trial — in the face of a changing virus,” said Stanley Erck, the president and chief executive of Novavax. He said that researchers expected the variants could change the trial results, but “the amount of change has been a bit of a surprise to everyone.” The South Africa trial was relatively small — with just 4,400 volunteers — and was not designed to come up with a precise estimate of how much protection the vaccine provides. Still, the results were striking enough that the company said it would soon begin testing a new vaccine tailored to protect against the variant from South Africa. “You’re going to have to make new vaccines,” Mr. Erck said. John Moore, a virologist at Weill Cornell Medicine who was not involved in the studies, praised the results. “Fifty percent is not as good as 100, but it’s a damn sight better than zero,” he said, noting that given the strong results in Britain, it was likely very similar in efficacy to the Pfizer and Moderna vaccines. While the Pfizer and Moderna vaccines rely on a newer mRNA technology that has not been used in previous vaccines, Novavax’s candidate employs an older, more established method that relies on injecting coronavirus proteins to provoke an immune response.  The fact that three vaccines all appeared to show lowered effectiveness against the variant from South Africa is not encouraging, and the results Novavax announced Thursday were the first to occur outside of a laboratory, testing how well a vaccine worked in people infected with a new variant. Johnson & Johnson is also on the cusp of announcing results of its Covid-19 vaccine trials, and has also tested its candidate in South Africa. The announcement from Novavax raises the stakes for Johnson & Johnson. The company was expected to announce its results as early as last weekend, and the delay has triggered speculation among scientists that the firm has also discovered that its vaccine worked less well in South African trial volunteers who were infected with the variant. In an earnings call on Tuesday, Alex Gorsky, the chief executive officer of the company, said they were looking forward to sharing results from their late-stage trial by early next week.

The emergence of several highly contagious variants has complicated efforts to bring the pandemic under control, leading world leaders to shut down travel to places like Britain and South Africa even as the variants already appear to have circled the globe. In the United States, researchers have warned that the variant first identified in Britain, which is believed to be more infectious, could become the dominant form of the virus in this country by March.  The United States is well behind other countries in testing for such variants, and the one from South Africa has been found in about 30 countries. But experts have also said there are reasons for optimism, noting that the vaccines remain effective. The best way to combat contagious new variants is to continue vaccination and other public health measures, which will slow the virus’s ability to infect new people and mutate further.  “This is really worrisome,” said Dr. Peter Hotez, a vaccine expert at the Baylor College of Medicine and the inventor of a coronavirus vaccine. “We have to have the American people vaccinated by late in the spring or early summer to have any hope in preventing the South African and the U.K. variants from taking over.” Drug makers could update their vaccines and offer new shots at regular intervals, similar to the flu vaccine.......

Novavax Press Release (Jan. 28, 2021):

https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3