RESULTS Of 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a ∼9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively.
CONCLUSIONS The fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development.
Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.
The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.
BioNTech Manufacturing GmbH (in partnership with Pfizer Inc.) submitted a Biologics License Application (BLA) STN BL 125742 for licensure of COVID-19 Vaccine, mRNA. The proprietary name of the vaccine is COMIRNATY. COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older. The vaccine is administered intramuscularly (IM) as a series of two 30 μg doses (0.3 mL each) 3 weeks apart.
For commentary, see FDA report finds all-cause mortality higher among vaccinated – Israel Nation News.
This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
Dr Bauer of the Francis Crick Institute explains that the Pfizer vaccine produces 5-6 times fewer neutralising antibodies that play a key role in protecting us from the Indian variant. He suggests that booster Pfizer jabs will be essential.
Levels of antibodies in the blood of vaccinated people that are able to recognise and fight the new SARS-CoV-2 Delta variant first discovered in India (B.1.617.2) are on average lower than those against previously circulating variants in the UK, according to new laboratory data from the Francis Crick Institute and the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre, published today (Thursday) as a Research letter in The Lancet.
The results also show that levels of these antibodies are lower with increasing age and that levels decline over time, providing additional evidence in support of plans to deliver a vaccination boost to vulnerable people in the Autumn.
In the case of single-dose recipients, our data show that NAbTs are significantly lower against B.1.617.2 and B.1.351 VOCs relative to B.1.1.7, implying that although a single dose might still afford considerably more protection than no vaccination, single-dose recipients are likely to be less protected against these SARS-CoV-2 variants. These data therefore suggest that the benefits of delaying the second dose, in terms of wider population coverage and increased individual NAbTs after the second dose,7 must now be weighed against decreased efficacy in the short-term, in the context of the spread of B.1.617.2. Worldwide, our data highlight the ongoing need to increase vaccine supply to allow all countries to extend second-dose protection as quickly as possible.
In the longer term, we note that both increased age and time since the second dose of BNT162b2 significantly correlate with decreased NAb activity against B.1.617.2 and B.1.351—both of which are also characteristic of the population in the UK at highest risk of severe COVID-19 (ie, older and vaccinated earlier), independent of other existing factors such as compromised immune status or comorbidity, or geographic-specific responses to vaccination.
A previously symptomless 86-year-old man received the first dose of the BNT162b2 mRNA COVID-19 vaccine. He died 4 weeks later from acute renal and respiratory failure. Although he did not present with any COVID-19-specific symptoms, he tested positive for SARS-CoV-2 before he died. Spike protein (S1) antigen-binding showed significant levels for immunoglobulin (Ig) G, while nucleocapsid IgG/IgM was not elicited. Acute bronchopneumonia and tubular failure were assigned as the cause of death at autopsy; however, we did not observe any characteristic morphological features of COVID-19. Postmortem molecular mapping by real-time polymerase chain reaction revealed relevant SARS-CoV-2 cycle threshold values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney and cerebrum) except for the liver and olfactory bulb. These results might suggest that the first vaccination induces immunogenicity but not sterile immunity.
Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. The present article uses clinical epidemiologic tools to critically appraise reports of efficacy in Pfzier/BioNTech and Moderna COVID-19 mRNA vaccine clinical trials. Based on data reported by the manufacturer for Pfzier/BioNTech vaccine BNT162b2, this critical appraisal shows: relative risk reduction, 95.1%; 95% CI, 90.0% to 97.6%; p = 0.016; absolute risk reduction, 0.7%; 95% CI, 0.59% to 0.83%; p < 0.000. For the Moderna vaccine mRNA-1273, the appraisal shows: relative risk reduction, 94.1%; 95% CI, 89.1% to 96.8%; p = 0.004; absolute risk reduction, 1.1%; 95% CI, 0.97% to 1.32%; p < 0.000. Unreported absolute risk reduction measures of 0.7% and 1.1% for the Pfzier/BioNTech and Moderna vaccines, respectively, are very much lower than the reported relative risk reduction measures. Reporting absolute risk reduction measures is essential to prevent outcome reporting bias in evaluation of COVID-19 vaccine efficacy.
A critical appraisal of phase III clinical trial data for the Pfizer/BioNTech vaccine BNT162b2 and Moderna vaccine mRNA-1273 shows that absolute risk reduction measures are very much lower than the reported relative risk reduction measures. Yet, the manufacturers failed to report absolute risk reduction measures in publicly released documents. As well, the U.S FDA Advisory Committee (VRBPAC) did not follow FDA published guidelines for communicating risks and benefits to the public, and the committee failed to report absolute risk reduction measures in authorizing the BNT162b2 and mRNA-1273 vaccines for emergency use. Such examples of outcome reporting bias mislead and distort the public’s interpretation of COVID-19 mRNA vaccine efficacy and violate the ethical and legal obligations of informed consent.