As the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to take a heavy toll on human health and life, new therapies and vaccines are being sought earnestly in an attempt to identify effective and safe ways to prevent and treat the disease.
However, the earliest vaccine to be approved for emergency use, the Pfizer/BioNTech BNT162b2 vaccine, appears to be highly effective and safe in protecting against the SARS-CoV-2 infection, including its relatively resistant beta variant B.1.351.
COVID-19 Vaccine. Image Credit: hedgehog94/Shutterstock.com
The BNT162b2 vaccine is a bit of viral messenger ribonucleic acid (mRNA) encoding full-length spike glycoprotein. The spike mRNA is engineered at nucleoside level, stabilized in the prefusion conformation, and is formulated as lipid nanoparticles.
As of now, more than 350 million doses of this vaccine have been administered worldwide. An earlier report by the same researchers focused on vaccine safety and efficacy at two months from immunization, in adults, finding a 95% vaccine efficacy (VE). It was also reported to be safe over a diverse study population.
This research led to its authorization on a conditional or emergency basis, worldwide. The current study reports the follow-up after up to six months of follow-up.
How was the study done?
The current research was carried out with a randomized, placebo-controlled single-blinded design, including healthy people with stable underlying illnesses. None had a history of COVID-19, though prior or current asymptomatic infection might be identified on testing.
There were over 45,000 participants at more than 150 sites internationally. All received two doses of the vaccine or placebo intramuscularly, at an interval of 21 days. Vaccine efficacy was evaluated by looking for laboratory-confirmed COVID-19 at 7 or more days after the second dose. The incidence was assessed separately in subjects with and without a history of prior infection.
Severe COVID-19 was also identified, and the viral lineages were reported in those without prior infection. Over half the participants were followed up for six or more months, with more than 80% being White. About a third were clinically obese, and a fifth had chronic underlying conditions.
There were over 2,200 12-15-year-olds participating in the study, with the same basic composition.
The study is published in the pre-print server medRxiv*.
What were the findings?
The study showed that almost 10,000 participants had reactions to the vaccine, including about 360 with earlier infection. Local reactions included mild or moderate pain at the site of infection, independent of prior infection. No severe local reactions were found.
Systemic events were more common in vaccine recipients, especially fatigue, mostly mild to moderate in intensity. They were found to occur more frequently after the first vaccine dose in those with a history of prior infection, relative to placebo. However, naïve vaccine recipients reported systemic events more often than those with prior infection, after dose 2.
Adverse events (AEs) that may be due to the vaccine include poor appetite, lethargy, weakness, and malaise, but serious AEs were rare, and no new events were reported after the first two-month report.
No deaths attributable to or related to the vaccine were reported in either group.
There were 77COVID-19 cases among 42,000 vaccine recipients aged 12 years or more, with onset at a week or more from the second dose, and without a history of prior infection. The corresponding incidence was 850 among placebo recipients. The vaccine efficacy is therefore 91%, irrespective of prior infection.
The protection conferred by natural infection was ~73%, as indicated by 1.3% and 4.7% attack rates among those placebo recipients who had or did not have antibodies to SARS-CoV-2 nucleoprotein at the time of entry into the study.
The VE with a single dose of BNT162b was ~58% but increased to ~92% from 11 days after the first dose up to the time of the second dose. The efficacy was highest between seven days to two months after dose 2, at ~96%.
Thereafter it declined to 90% by four months, and ~84% by the end of the study.
Gratifyingly, the protection afforded by the vaccine against severe disease, beginning from the first dose, was ~97%. Also, there was no significant difference in VE by race, sex, ethnic origin, or underlying conditions.
The beta variant has been reported to be partially resistant to neutralization by antibodies elicited by this vaccine, compared to other lineages. However, it was seen to be 100% effective in preventing COVID-19 caused by this variant, as shown by the identification of B.1.351 lineage in all nine nasal samples collected from COVID-19-positive placebo recipients in South Africa. There were no cases among vaccine recipients.
What are the implications?
The study serves to bring BNT162b2 vaccine safety and efficacy data up to date, indicating that it protects individuals of 12 years and up against the virus, reducing the incidence of infection by 91%, and of severe disease by 97%. This protection kicks in from about the 11th day after the first dose, providing 92% protection until the second dose is taken.
During this period, neutralizing antibody titers have been reported to be undetectable or low, though non-neutralizing binding antibodies rise. The high degree of early protection seen despite these findings suggest that serum neutralizing antibodies are inadequate to explain it. Conversely, innate immunity, T and B cell responses, and antibody-dependent cytotoxicity may all take part in this phase of protection.
The decline in efficacy from 97% soon after the second dose to 84% indicates a 6% fall over each two-month interval. Continued follow-up is planned for two years, and may provide answers as to whether this decline will continue over time, and if it will make a third booster necessary, as well as when such a dose should be administered. Real-world data will supplement this experimental observation.
Reassuring evidence that the BNT162b2 vaccine retained high efficacy against the beta variant was also forthcoming.
Our studies of in vitro neutralization of a variety of SARS-CoV-2 variants have, to date, found that all tested BNT162b2-immune sera neutralize all tested variants.”
The safety profile in patients as young as 12 years, as well as the absence of any indication to test for prior infection before vaccination, are additional implications of the findings of this study.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.