Virus World

Comparison of the immune response to four prominent COVID-19 vaccines is among the most thorough so far, authors say.  A rare head-to-head comparison shows that the COVID-19 vaccines made by Pfizer and Moderna outperform those from Johnson & Johnson and Novavax1. The data also provide a finely detailed picture of the immune protection that each vaccine offers — information that could be useful for designing future vaccines. The research was posted on the preprint server bioRxiv on 21 March. It has not yet been peer reviewed. The study assessed the 4 vaccines using 14 metrics, including levels of several types of immune cell such as T cells and B cells, as well as immune molecules called neutralizing antibodies. Such investigations are sorely needed to sort through the flood of COVID-19 vaccines in the research pipeline and on the market, researchers say. “It’s a really nice analysis by premier immunologists that builds upon what has been previously shown,” says Robert Seder, an immunologist at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.  Previous comparisons of COVID-19 vaccines have often brought together data from different studies, which might have been conducted with slightly varying laboratory techniques. For the latest study, by contrast, researchers applied the same techniques across all the vaccines they investigated. “When you try to compare [vaccine data] between different papers, which is what many of us have been doing for over a year now, you get apples to oranges comparisons, and you can be way off,” says Shane Crotty, an immunologist at La Jolla Institute for Immunology in California and a co-author of the preprint. The four vaccines that Crotty and his co-authors examined fall into three classes. The jabs made by Moderna in Cambridge, Massachusetts, and by Pfizer in New York City and BioNTech in Mainz, Germany, are both based on messenger RNA. Johnson & Johnson (J&J) of New Brunswick, New Jersey, has produced a ‘viral vector’ vaccine that uses a harmless virus to deliver SARS-CoV-2 genetic material into host cells. The vaccine made by Novavax in Gaithersburg, Maryland, contains pieces of the SARS-CoV-2 spike protein.

Strengths and weaknesses

Antibody levels induced by two doses of Pfizer’s or Moderna’s mRNA vaccine tended to wane substantially over six months. By contrast, antibody levels from J&J’s one-shot vaccine were stable or even increased over time. But antibody levels measured six months after vaccination with the J&J jab were still lower than those observed six months after vaccination with an mRNA vaccine. Novavax’s two-shot regimen induced antibody responses on a par with those to the mRNA vaccines. However, after the Novavax jab, levels of CD8+ T cells, which destroy infected cells, were low to undetectable, whereas the other three vaccines performed well in this metric. These results generally support the findings of previous studies. But the latest research offers a more extensive analysis of the immune system’s response than do earlier studies, and uses an apples-to-apples approach. 

No losers

“This is not meant to proclaim winners and losers,” says study co-author Alessandro Sette, an immunologist at La Jolla. Instead, the study is meant to “provide a comprehensive evaluation of the different variables”, he says. Novavax has received authorization for its vaccine in 38 countries. The vaccines made by Moderna, Pfizer and J&J have all received wide authorization globally. One caveat is that the study looked at the effects of the Novavax jab in only 12 people. It examined the other three vaccines in 30 volunteers each. Seder notes that the analysis considers the effects of only a two-dose regimen of the mRNA vaccines. It does not consider the protection provided by boosters, because the authors began the work in late 2020, before a third shot was recommended by health authorities. Crotty, Sette and their colleagues are now conducting a similar head-to-head study that includes mRNA boosters.

Cited research available at bioRxiv (March 21, 2022):

https://doi.org/10.1101/2022.03.18.484953  

Vaccine effectiveness against COVID-19 hospitalization among U.S. adults without immunocompromising conditions was highest for the Moderna vaccine compared with the other two available COVID-19 vaccines, researchers reported in MMWR. “Three COVID-19 vaccines are authorized or approved for use among adults in the United States,” Wesley H. Self, MD, associate professor at the Vanderbilt University School of Medicine, and colleagues wrote. “Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for a specific vaccine.” To better assess vaccine effectiveness (VE) of the three available COVID-19 vaccines in the U.S. in preventing COVID-19 hospitalization, Self and colleagues conducted a case-control analysis among 3,689 adults aged 18 years and older who were hospitalized at 21 U.S. hospitals between March 11 and Aug. 15, 2021.

According to the study, an additional analysis compared serum antibody levels to SARS-CoV-2 among 100 healthy volunteers enrolled at three hospitals 2 to 6 weeks after full vaccination with the Moderna, Pfizer-BioNTech or Johnson & Johnson vaccines. Overall, the study demonstrated that VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% CI, 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI, 85%-91%), whereas VE for both of the messenger RNA vaccines was higher than that of the Johnson & Johnson vaccine (71%; 95% CI, 56%-81%). Additionally, the study showed that protection from the Pfizer-BioNTech vaccine declined 4 months after vaccination. Researchers added that post-vaccination anti-spike IgG and anti-receptor binding domain IgG levels were significantly lower in participants who were vaccinated with the Johnson & Johnson vaccine compared with the Moderna or Pfizer-BioNTech vaccines.

Research cited published in MMWR (Sept.17, 2021):

 http://dx.doi.org/10.15585/mmwr.mm7038e1 

With concerns surrounding the Delta coronavirus variant rising globally, how effective are the current vaccines in the U.S. at protecting against the new version of the virus? According to medical experts, the three vaccines currently available each offer protection. Here’s a breakdown of each vaccine and what you should know: How effective are the COVID vaccines overall? In clinical trials, Moderna’s  In clinical trials, Moderna's vaccine reported 94.1% effectiveness at preventing COVID-19 in people who received both doses. The Pfizer-BioNTech vaccine was said to be 95% effective. A new CDC study reported that a single dose of Pfizer's or Moderna's COVID vaccine was 80% effective in preventing infections. That number jumped to 90% two weeks after the second dose, the study on vaccinated health care workers showed.  "These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions," the U.S. agency wrote in the study. "COVID-19 vaccination is recommended for all eligible persons." Pfizer's vaccine, the only one currently authorized for use in children as young as 12, also showed heightened effectiveness among adolescents.  Pfizer in late March released preliminary results from a vaccine study of 2,260 U.S. volunteers ages 12 to 15, showing there were no cases of COVID-19 among fully vaccinated adolescents compared with 18 among those given dummy shots. More intriguing, researchers found the kids developed higher levels of virus-fighting antibodies than earlier studies measured in young adults. The FDA said J&J’s vaccine offers strong protection against what matters most: serious illness, hospitalizations and death. One dose was 85% protective against the most severe COVID-19 illness, in a massive study that spanned three continents — protection that remained strong even in countries such as South Africa, where the variants of most concern were spreading at the time.  The CDC reports J&J/Janssen vaccine was 66.3% effective in clinical trials at preventing COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. "The vaccine had high efficacy at preventing hospitalization and death in people who did get sick," the CDC notes. "No one who got COVID-19 at least four weeks after receiving the J&J/Janssen vaccine had to be hospitalized." It is not known if any of the three vaccines prevent the spread of the virus by people who are asymptomatic, though the CDC noted that "early evidence suggests that the J&J/Janssen vaccine might provide protection against asymptomatic infection." 

How effective are the vaccines against the new Delta variant?

Data surrounding vaccine effectiveness with the Delta variant is so far limited. While studies have shown that the available vaccines work against variants, including the Delta variant, all two-dose vaccines offer significantly more protection following their second dose. Researchers in England studied how effective the two-dose AstraZeneca and Pfizer-BioNTech vaccines were against it, compared with the Alpha variant that was first detected in the U.K. The vaccines were protective for those who got both doses but were less so among those who got one dose. One recent study showed the Pfizer vaccine was 84% effective against the variant after two doses, but only 34% effective after the first dose.  Moderna also announced Tuesday that a new study showed its vaccine also produced promising protection in a lab setting against the Delta variant and others currently circulating. “As we seek to defeat the pandemic, it is imperative that we are proactive as the virus evolves. We remain committed to studying emerging variants, generating data and sharing it as it becomes available. These new data are encouraging and reinforce our belief that the Moderna COVID-19 Vaccine should remain protective against newly detected variants,” Stéphane Bancel, chief executive officer of Moderna, said in a statement. Currently, little data has been released showing just how effective the Johnson & Johnson is at protecting against the Delta variant, though it is believed that the single-shot vaccine does offer protection against the variant. Dr. Scott Gottlieb, former Food and Drug Administration commissioner, reportedly said the Johnson & Johnson vaccine appears to be about 60% effective against the Delta variant. Still, medical experts say any of the three vaccines currently being used in the U.S. continue to show good results as far as protection. ”This will protect them against getting very sick and being hospitalized and even dying from the Delta variant,” Dr. Katherine Gergen-Barnett of Boston Medical Center recently told NBC10 Boston.

Will a booster shot be needed?

So far, there has been no recommendation from the Centers for Disease Control and Prevention surrounding booster shots with the Delta variant. Still, health experts have repeatedly cautioned that COVID-19 booster shots could be needed for fully vaccinated people, particularly as new variants spread. White House chief advisor Dr. Anthony Fauci said during an interview with MSNBC's Medhi Hasan in April that people may need to get booster shots in a year.  Pfizer CEO Albert Bourla also previously said people will "likely" need a third dose within 12 months of getting fully vaccinated.  So far, studies suggest that the vaccines currently in use can recognize the emerging variants — but they may not provide quite as much protection against the new strains. Boosters and new versions of vaccines that target the variants are already being explored. Pfizer-BioNTech was previously testing a third booster shot of its vaccine on fully vaccinated people.   "The flexibility of our proprietary mRNA vaccine platform allows us to technically develop booster vaccines within weeks, if needed," Sahin said in a release in February. Moderna was also testing a potential third dose of its current vaccine, and a possible booster shot specifically targeting the South Africa variant. Citing early data, the company recently said the booster vaccine generated a promising immune response against the B.1.351 and P.1 variants first identified in South Africa and Brazil, respectively. Meanwhile, Johnson & Johnson CEO Alex Gorsky said during an interview with CNBC's "Squawk Box" in March that the company is well-positioned to adapt its vaccine for variants, and is working on developing software that will "help address some of these new and emerging variants."

The White House is eager to project progress, but the public-private partnership it has created still faces scientific hurdles, internal tensions and questions from Congress. The Trump administration has selected five companies as the most likely candidates to produce a vaccine for the coronavirus, senior officials said, a critical step in the White House’s effort to deliver on its promise of being able to start widespread inoculation of Americans by the end of the year. By winnowing the field in a matter of weeks from a pool of around a dozen companies, the federal government is betting that it can identify the most promising vaccine projects at an early stage, speed along the process of determining which will work and ensure that the winner or winners can be quickly manufactured in huge quantities and distributed across the country. The announcement of the decision will be made at the White House in the next few weeks, government officials said. Dr. Anthony S. Fauci, the federal government’s top epidemiologist and director of the National Institute of Allergy and Infectious Diseases, hinted at the coming action on Tuesday when he told a medical seminar that “by the beginning of 2021 we hope to have a couple of hundred million doses.”

The five companies are Moderna, a Massachusetts-based biotechnology firm, which Dr. Fauci said he expected would enter into the final phase of clinical trials next month; the combination of Oxford University and AstraZeneca, on a similar schedule; and three large pharmaceutical companies: Johnson & Johnson, Merck and Pfizer. Each is taking a somewhat different approach...

All three currently authorized COVID-19 vaccines still showed signs of a strong immune response eight months later without a booster, according to a study published Friday in the New England Journal of Medicine. The study analyzed specific markers of immunity found in the blood of people vaccinated with Pfizer, Moderna and the Johnson & Johnson vaccines.  Echoing evidence from the real world, researchers found cellular signatures suggesting that all three vaccines produce strong and long-lasting protection from severe illness. But the analysis also hinted at differences in the way the vaccines produce antibodies -- with Pfizer and Moderna antibodies spiking and then fading quickly, while Johnson & Johnson antibodies started at a lower level but remained more stable over time.  "By month eight, antibody responses were comparable for these three vaccines," said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, who coauthored the research. Pfizer and Moderna vaccines rely on the same type of technology, called mRNA, while Johnson & Johnson uses a different technology, called viral vector. The two technologies prompt different types of immune responses. Thought the pandemic, scientists have used antibodies -- virus fighting proteins in the blood -- as one indication that vaccines are working. But antibodies are only one part of the body's overall immune response.

This new study is among the first to directly compare not just antibodies, but also T-cells, across all three vaccines. T-cells are also a crucial part of the immune system, and may offer longer-lasting protection even after antibodies fade. "We think the antibodies are often more relevant preventing against infection, and the T-cells are more relevant killing the virus -- so preventing severe disease," said Dr. Todd Ellerin, director of infectious diseases at South Shore Health and an ABC News medical contributor. "T-cell responses likely contribute to vaccine protection against severe disease," said Barouch. "T-cell responses were relatively stable for all three vaccines for eight months." This new study is among the first to directly compare not just antibodies, but also T-cells, across all three vaccines. T-cells are also a crucial part of the immune system, and may offer longer-lasting protection even after antibodies fade. "We think the antibodies are often more relevant preventing against infection, and the T-cells are more relevant killing the virus -- so preventing severe disease," said Dr. Todd Ellerin, director of infectious diseases at South Shore Health and an ABC News medical contributor. "T-cell responses likely contribute to vaccine protection against severe disease," said Barouch. "T-cell responses were relatively stable for all three vaccines for eight months."

Original findings published in NEJM (October 15, 2021):

https://doi.org/10.1056/NEJMc2115596

• COVID-19 vaccines from Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca all have unique features.
• They varyin effectiveness, side effects, dosage, and ages approved for the shots.
• Here is a table that compares them all. Scroll down to view it.

Coronavirus vaccines are the world's escape route out of a pandemic that has shut down schools, grounded flights, and left millions dead. Vaccines from Moderna, Pfizer-BioNTech, AstraZeneca-Oxford University, and Johnson & Johnson have been approved in the West. In the US, all of them have been authorized except AstraZeneca's — in the UK, all of them except Johnson & Johnson's are authorized. Each is given as a shot in the muscle of the upper arm. You might not get a choice about which COVID-19 vaccine you get, but all four offer some protection against severe illness, so the advice is to take one if you are offered it. For the two-dose vaccines, you should have two shots of the same one, where possible.  Speak with your doctor if you are pregnant, breastfeeding, have a specific medical condition, or take medicines —especially if they thin your blood or affect your immune system. Experts have said the COVID-19 vaccines won't make you infertile. Side effects may start within a day or two and should go away within a few days.  We've made a table that gives you the key information for each shot, whether you've booked an appointment or not. Scroll down to view it.