Virus World

The bivalent vaccine will now form part of the booster campaign to be rolled out this autumn.  Ministers say the vaccine will now form part of the autumn booster campaign. Moderna thinks 13 million doses of its new vaccine will be available this year, but 26 million people are eligible for some form of booster. Health officials say people should take whichever booster they are offered as all jabs provide protection. The original vaccines used in the pandemic were designed to train the body to fight the first form of the virus which emerged in Wuhan, in China, at the end of 2019. The Covid virus has since mutated substantially, with a stream of new variants emerging that can dodge some of our immune defences. They have caused large surges in cases around the world. The original vaccines still provide strong protection against becoming severely ill or dying, but companies are tweaking them to match the virus as it evolves. Cases of coronavirus are currently falling in the UK. In mid-to-late July, around 2.5 million people tested positive for coronavirus.

Vaccination and Household Transmission of SARS-CoV-2 In this study involving household contacts of persons with laboratory-confirmed Covid-19, the risk of household transmission was 40 to 50 lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevents infection and reduces the severity of coronavirus disease 2019 (Covid-19) in vaccinated persons.1,2 We investigated whether vaccination would reduce transmission in the household setting in the context of postvaccination infection. We analyzed data from the Household Transmission Evaluation Dataset (HOSTED), which has information on all laboratory-confirmed cases of Covid-19 in England and in which data on all persons sharing the same address are linked.3 We then linked to individual-level data on all Covid-19 vaccinations in England (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). We compared the risk of secondary infection (defined as a positive SARS-CoV-2 test 2 to 14 days after the positive test for the index case) among unvaccinated household contacts of persons with SARS-CoV-2 infection who had received at least one dose of the ChAdOx1 nCoV-19 or BNT162b2 vaccine 21 days or more before testing positive with the risk among unvaccinated household contacts of unvaccinated persons with infection. We fitted logistic-regression models with adjustment for the age and sex of the person with the index case of Covid-19 (index patient) and the household contact, geographic region, calendar week of the index case, deprivation (a composite score of socioeconomic and other factors), and household type and size. We also considered the timing of effects among index patients who had been vaccinated at any time up to the date of the positive test.

Between January 4 and February 28, 2021, there were 960,765 household contacts of unvaccinated index patients, and there were 96,898 secondary cases of Covid-19 (10.1%). (Descriptive data regarding the index patients and their household contacts are provided in the Summary Results section.) The numbers of secondary cases according to the vaccination status of the index patient, and the results of logistic-regression models, are shown in Table 1. Overall, the likelihood of household transmission was approximately 40 to 50% lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients; the findings were similar for the two vaccines. Most of the vaccinated index patients in our data set (93%) had received only the first dose of vaccine. Assessment of infection risks among household contacts according to the timing of vaccination of the index patient showed protective effects when the vaccine had been administered at least 14 days before the positive test (Figs. S1 and S2 in the Supplementary Appendix)....

Published in NEJM (June 23, 2021):

https://doi.org/10.1056/NEJMc2107717 

Sage says majority were likely infected shortly before or soon after jab, before immunity had time to develop.  One in 25 people hospitalised with Covid-19 since December have had at least one dose of vaccine, with the majority infected shortly before or soon after vaccination – before immunity would have had time to develop. However, few of those who developed symptoms, did so more than 2 weeks after receiving a first dose – indicating that the vaccines do help to prevent serious disease once they’ve had time to take effect. The data, presented to the government’s Scientific Advisory Group for Emergencies (Sage), could be a further indication that people are dropping their guard once they’ve received a jab, wrongly assuming that they are immediately protected. Alternative explanations include the possibility that they were infected shortly before vaccination, during the vaccine appointment itself, or that vaccination triggered symptoms in infected people who were previously asymptomatic. In minutes from its 83rd meeting on 11 March Sage said:“The observation that a significant number of people developing symptoms within a few days of a first dose may suggest some behaviour change following vaccination. It is important therefore that communications around vaccination reinforce the need for safe behaviours to be maintained.” Almost 29 million people in the UK have received at least one dose of a coronavirus vaccine so far, with some degree of immune protection thought to develop around two weeks after receiving the first jab – although a second dose is needed to achieve the highest levels of protection.

According to data submitted to Sage by the Covid-19 Clinical Information Network (CO-CIN), there were 1,802 recorded cases of vaccinated patients hospitalised with Covid-19 in the UK as of 5 March. This accounted for 4.2% (1,802/42,788) of all Covid-related hospital admissions since 8 December – the date when the first people in the UK were vaccinated. The median time between vaccination and symptom onset for these patients was five days, indicating that most of them were infected shortly before or around the time of vaccination, with the remainder infected after vaccination but before immunity had developed. “Elderly and vulnerable people who had been shielding, may have inadvertently been exposed and infected either through the end-to-end process of vaccination, or shortly after vaccination through behavioural changes where they wrongly assume they are immune,” the CO-CIN report said.  Data from previous vaccine rollouts, national surveys and evidence from Israel have also indicated that people may be less likely to abide by social distancing rules once they’ve been vaccinated. In its 11 March meeting, Sage emphasised the need for better government communication about how long it takes for the jab to work, and that although the Covid-19 vaccines in use in the UK are highly effective, no vaccine is 100% effective. Minutes from the meeting said: “Some people will be hospitalised with Covid-19 even after completing their full vaccination schedule. It will be particularly important to monitor the prevalence of different variants present in this group by sequencing to understand any potential immune escape. This is under way by Public Health England.” A separate document released by Sage on Friday suggested there has been a four-fold increase in confirmed cases of the Brazilian P1 variant during the fortnight of 10 March to 24 March from 5 to 21, while cases of the South African variant have increased from 190 to 305.

Novavax Inc's COVID-19 vaccine was 96% effective in preventing cases caused by the original version of the coronavirus in a late-stage trial conducted in the United Kingdom, the company said on Thursday, moving it a step closer to regulatory approval.  There were no cases of severe illness or deaths among those who got the vaccine, the company said, in a sign that it could stop the worse effects of new variants that have cropped up. The vaccine was 86% effective in protecting against the more contagious virus variant first discovered and now prevalent in the United Kingdom, for a combined 90% effectiveness rate overall based on data from infections of both versions of the coronavirus. Novavax shares jumped 22% in after-hours trading to $229. They were trading below $10 on Jan. 21, 2020, when the company announced it was developing a coronavirus vaccine. In a smaller trial conducted in South Africa - where volunteers were primarily exposed to another newer, more contagious variant widely circulating there and spreading around the world - the Novavax vaccine was 55% effective, based on people without HIV, but still fully prevented severe illness.  Novavax Chief Medical Officer Filip Dubovsky said the performance in South Africa suggests there may still be a case for using it in areas where the South African variant is dominant.

Novavax is also developing new formulations of its vaccine to protect against emerging variants and plans to initiate clinical testing of these shots in the second quarter of this year. Results from the final analysis of the UK trial were largely in line with interim data released in January. The company expects to use the data to submit for regulatory authorization in various countries. It is not clear when it will seek U.S. authorization or if regulators will require it to complete an ongoing trial in the United States. Novavax expects data from a 30,000-person trial in the United States and Mexico by early April. Dubovsky said that Novavax is still planning to file for authorization from UK regulators early in the second quarter of 2021.  The UK trial, which enrolled more than 15,000 people aged 18 to 84, assessed efficacy of the vaccine during a period with high transmission of the UK virus variant now circulating widely.

The shot’s effectiveness in the South Africa trial declined to around 49% when the analysis included data from HIV-positive participants. The vaccine could be cleared for use in the United States as soon as May if U.S. regulators decide the UK data is enough to make a decision. It could take a couple months longer if they insist on first seeing data from the U.S. trial, its chief executive told Reuters earlier this month. “Ultimately, they have to decide whether the data we can bring to the table is adequate or whether they would prefer to wait on data from our U.S. study,” Dubovsky said on Thursday. Novavax’s vaccine production plants should all be fully functional by April, executives said on a March investor call. The drugmaker expects to have tens of millions of doses stockpiled and ready to ship in the United States when it receives authorization, CEO Stanley Erck told Reuters.  Novavax plans to produce its two-shot vaccine at eight manufacturing locations, including the Serum Institute of India. If authorized, it would follow three COVID-19 vaccines previously approved for use in Britain from Pfizer and partner BioNTech, Moderna Inc and the AstraZeneca shot developed with Oxford University. The Maryland-based company has received $1.6 billion from the U.S. government in funding for the vaccine trial and to secure 100 million doses.

The University of Oxford will lead the first trial exploring whether different Covid-19 vaccines can be used interchangeably, the University’s vaccine group said Thursday, an effort that could make vaccination programs more flexible and even provide better protection against the disease.  The study, run by the U.K. National Immunisation Schedule Evaluation Consortium, will recruit over 800 people over the age of 50 to evaluate the feasibility of using one vaccine for the first “prime” shot and different one for the second “booster” shot. At first, the trial will use the Oxford-AstraZeneca and Pfizer-BioNTech vaccines, both already cleared for emergency use in the U.K., with others potentially being added at a later date.  Britain’s Deputy Chief Medical Officer, Jonathan Van-Tam, said the trial would offer "greater insight" into the use of vaccines against Covid-19, and provide data that could support a “more flexible immunization programme" in light of global supply chain issues. 

AstraZeneca Plc said on Sunday Britain's health regulator had started an accelerated review of its potential coronavirus vaccine. “We confirm the MHRA’s (Medicines and Healthcare Products Regulatory Agency) rolling review of our potential COVID-19 vaccine,” an AstraZeneca spokesman said. In rolling reviews, regulators are able to see clinical data in real time and have dialogue with drug makers on manufacturing processes and trials to accelerate the approval process. The approach is designed to speed up evaluations of promising drugs or vaccines during a public health emergency. AstraZeneca’s COVID-19 vaccine is being developed along with the University of Oxford. Bloomberg reported on Friday that MHRA had also begun an accelerated review for the COVID-19 vaccine candidate from Pfizer Inc. AstraZeneca and Pfizer are among the frontrunners in the race to develop a vaccine for the coronavirus, with the race also including Johnson & Johnson and Moderna Inc. Their vaccine candidates are in late-stage trials, interim data from which are expected in the coming weeks.

The British drug maker said on Monday its COVID-19 experimental vaccine produces an immune response in both old and young adults. The vaccine also triggers lower adverse responses among the elderly, it said.  The novel coronavirus has killed more than 1.19 million people globally, damaged the world economy and turned normal life upside down for billions of people. Work began on the Oxford vaccine in January. Called AZD1222 or ChAdOx1 nCoV-19, the viral vector vaccine is made from a weakened version of a common cold virus that causes infections in chimpanzees.

ONS figures show 51,281 Covid deaths between January and July, with 458 dying at least 21 days after second dose.  People who were fully vaccinated accounted for just 1.2% of all deaths involving Covid-19 in England in the first seven months of this year. The figures, published by the Office for National Statistics (ONS), have been seized on as proof of the success of the vaccine programme. The figures show a total of 51,281 deaths involving Covid-19 in England between 2 January and 2 July, of which 38,964 were of unvaccinated people.  Of the total Covid-related deaths, 458 (about 0.9%) were of people who died at least 21 days after their second vaccine dose. Just 256 deaths (0.5%) were of people who were fully vaccinated and had their first positive PCR test at least 14 days after their second dose. No vaccine is 100% effective against Covid-19, and health authorities have made it clear that some deaths of vaccinated individuals are to be expected. Public Health England (PHE) has estimated that two-dose effectiveness against hospital admission with infections from the Delta variant – which is now the UK’s dominant strain – has been around 94%.  However, the figures on Monday underlined that the risk of death involving Covid-19 is consistently lower for people who have received two doses compared with one dose or no vaccination at all.

A detailed breakdown of data was made available for 252 of the 256 people who died after having received both jabs and who first tested positive at least 14 days after the second dose. They are what the ONS describes as “breakthrough” deaths. It shows that just over three-quarters of these deaths (76.6%) occurred in those who were clinically extremely vulnerable – a slightly higher proportion than for other Covid-19 deaths (74.5%) and deaths not involving Covid-19 (69.7%). Of the breakthrough deaths, 61.1% occurred in males, which is higher than for other Covid-19 deaths (52.2%) and deaths not involving Covid-19 (48.5%), while 13% were among people who were immunocompromised. Experts emphasised the importance of context in terms of the data, which covered a period when the seven-day average daily UK deaths varied between six and more than 1,200 per day. Trends were increasing at the end of the ONS study period, when rates were about 25 per day, while daily death rates are now consistently over 100 per day.  Dr Duncan Robertson, a data analyst at Loughborough University who has been focusing on Covid-19 modelling and analysis, said: “By definition, as the proportion of vaccinated people increases, fewer remain in the unvaccinated category. In the extreme, if everyone were vaccinated, 100% of deaths would be of vaccinated people, just as before the vaccine rollout, 0% of deaths would be of vaccinated people.” But he added: “What is clear from the ONS data is the significance of being fully vaccinated – full vaccination offers very high – but not perfect - protection against death, where only having a first dose offers significantly less protection.”

A single dose of the COVID-19 vaccine made by either Pfizer or AstraZeneca cuts a person’s risk of transmitting SARS-CoV-2 to their closest contacts by as much as half, according to an analysis of more than 365,000 households in the United Kingdom. Although the vaccines have been shown to reduce COVID-19 symptoms and serious illness, their ability to prevent coronavirus transmission has been unclear. Kevin Dunbar, Gavin Dabrera and their colleagues at Public Health England in London looked for cases in which someone became infected with SARS-CoV-2 after receiving a dose of either vaccine (R. J. Harris et al. Preprint at Knowledge Hub https://go.nature.com/3e3iu1i; 2021). They then assessed how often those individuals transmitted the virus to household contacts. The team found that people who had been vaccinated for at least 21 days could still test positive for the virus. But viral transmission from these individuals to others in their households was 40–50% lower than transmission in households in which the first person to test positive had not been vaccinated. Results for the two vaccines were similar. The findings have not yet been peer reviewed.

Background: Following a single dose of BNT162b2 mRNA vaccine, higher antibody titres are observed following prior SARS-CoV-2 infection than in infection-naive individuals, but T-cell responses are less well defined.

Methods: We sampled healthcare workers (HCWs) enrolled in the UK PITCH study, before and after BNT162b2 mRNA vaccination. We measured spike-specific antibody, and quantified T-cell responses by IFNγ ELISpot assay and intracellular staining of peripheral blood mononuclear cells (PBMC), comparing SARS-CoV-2-naïve individuals to those with prior infection.

Findings: HCWs aged 22 to 71 years received one (n=216) or two (n=21) vaccine doses. After a single dose, the spike-specific T-cell response was six-fold higher in previously-infected vs. naive individuals (median 340 vs. 58 SFU/106 PBMC, p<0.0001; fresh PBMC, n=99). The T-cell response in previously-infected individuals after one vaccine dose was equivalent to naïve individuals receiving two vaccine doses (median 158 vs. 165 SFU/106 PBMCs, p=0.65; cryopreserved PBMC, n=117). Anti-spike IgG levels following a single dose in those previously infected (median 512.9 antibody units/ml (AU/ml)) were 6.8-fold higher vs. naïve individuals following one dose (median 75.0 AU/ml, p<0.0001) and 2.9-fold higher than naïve individuals given two doses three weeks apart (179.9 AU/ml, p=0.03). Following vaccination, plasma from individuals with prior infection demonstrated higher in vitro neutralisation of the B.1.351 variant of concern compared to naive individuals.

Interpretation: Following a single BNT162b2 dose, HCWs with a prior history of SARS-CoV-2 infection have significantly higher T-cell and antibody responses than naive individuals.Funding UK Department of Health and Social Care and UK Coronavirus Immunology Consortium.

Available as preprint in The Lancet (March 25, 2021):

http://dx.doi.org/10.2139/ssrn.3812375 

Rapid approval without lengthy tests can happen if new vaccines are needed to fight variants, say regulators.  Current vaccines may not work as well against some variants and scientists are working on updating them now. But manufacturers will not need to seek brand new approval or do lengthy clinical studies. However they will need proof that the shots trigger protective antibodies in the blood. The aim is to shorten the process, where possible, so that vaccine approval could happen in weeks and months, not years. A similar fast-track method is already used for annual flu vaccines which regularly need updating to keep up with a virus that is constantly changing by mutating. The MHRA has issued guidance, along with authorities in Australia, Canada, Singapore and Switzerland, on what checks and measures would be necessary. The coalition of regulators - the ACCESS Consortium - insist no corners will be cut, with safety paramount.

NEW YORK: Pfizer and BioNTech's COVID-19 vaccine appeared to only lose a small bit of effectiveness against an engineered virus with three key mutations from the new variant found in South Africa, according to a laboratory study conducted by the US drugmaker. The study by Pfizer and scientists from the University of Texas Medical Branch (UTMB), which has not yet been peer-reviewed, showed a less than two-fold reduction in antibody titer levels, indicating the vaccine would likely still be effective in neutralising a virus with the so-called E484K and N501Y mutations found in the South African variant. The study was conducted on blood taken from people who had been given the vaccine. Its findings are limited, because it does not look at the full set of mutations found in the new South African variant. The scientists are currently engineering a virus with the full set of mutations and expect to have results from that in about two weeks, according to Pei-Yong Shi, an author of the study and a professor at UTMB.

The results are more encouraging than another non-peer reviewed study from scientists at Columbia University earlier on Wednesday which used a slightly different method and showed antibodies generated by the shots were significantly less effective against the South Africa variant. One possible reason for the difference could be that the Pfizer findings are based on an engineered coronavirus, and the Columbia study used a pseudovirus based on the vesicular stomatitis virus, a different type of virus, UTMB's Shi said.  He said he believes that finding in pseudoviruses should be validated using the real virus. The study also showed even better results against several key mutations from the highly transmissible UK variant of the virus. Shi said they were also working on an engineered virus with the full set of mutations from that variant as well.

Research cited available in bioRxiv (Jan. 27, 2021):

https://doi.org/10.1101/2021.01.27.427998