Researchers have been working at record speed to develop vaccines to contain the pandemic with coronavirus disease 2019 (COVID-19), which has been caused by a new coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several COVID-19 vaccines, based on different technologies, have received emergency use authorization (EUA) from global regulatory bodies.
However, all available vaccines are designed to work against SARS-CoV-2 peak protein of the original strain as an antigen.
Despite the fact that all COVID-19 vaccines show a significant reduction in the disease burden in clinical trials, the development of more effective vaccines is urgently needed in view of the emergence of more virulent and transmissible SARS-CoV-2 variants, evasion of the vaccine -induced immune response as well as high global demand for vaccines.
A SARS-CoV-2 vaccine, namely NVX-CoV2373 (Novavax), has been developed using full-length, prefusion-stabilized, recombinant spike protein trimer generated from the Wuhan-Hu-1 sequence. This engineered tip protein was assembled into nanoparticles and co-formulated with a saponin-based adjuvant (Matrix-M). This vaccine has been reported to be stable at a temperature of 2 to 8 ° C; therefore, it can be easily stored in refrigerators. Researchers believe that this vaccine can effectively solve the global problem of vaccine deficiency and deal with SARS-CoV-2 infection.
Previous studies have reported that NVX-CoV2373 is safe and immunogenic in adults. The current study showed that it has a high effect against serious disease caused by B.1.351 (the Beta variant), in a phase 2b trial in South Africa. Similarly, this vaccine was found to be effective against severe infection caused by the Alpha variants and was evaluated in phase three clinical trials in the United Kingdom.
A new study
A new study, published in New England Journal of Medicine, has described the results of PREVENT-19 (Prefusion Protein Subunit vaccine Efficacy Novavax Trial-COVID-19), a Phase 3 trial of NVX-CoV2373 that included all adults in the United States and Mexico. This study was conducted during a period when the circulating variants were predominantly Alpha, Beta, Gamma, B.1.427 and Epsilon and Iota.
Researchers conducted a randomized, controlled trial to determine the efficacy and safety of an adjuvanted SARS-CoV-2 recombinant spike protein vaccine in a study cohort consisting of approximately 30,000 participants from the United States and Mexico. Researchers continued to assess the duration of protection in a blinded crossover manner and measured the overall safety profile of the vaccine among participants.
About the study
The current study revealed a high (90%) short-term vaccine efficacy of NVX-CoV2373 against COVID-19 infection and 100% efficacy to prevent moderate to severe disease. Researchers found that the vaccine was absolutely safe during a median safety follow-up of 2 months with mild to moderate transient reactogenicity. A long-term assessment of the vaccine’s safety is planned, ie. participants will be monitored frequently 24 months after the first vaccination.
The current lawsuit also decides the effectiveness of NVX-CoV2373 in the evolving pandemic. This vaccine showed a vaccine efficacy of more than 90% against the circulating variants in the United States and Mexico, which are largely represented by the Alpha variant. The results of this study are consistent with phase three trials conducted in the UK that reported 86.3% vaccine efficacy. In addition, this vaccine showed high efficacy against other SARS-CoV-2 variants that have not been classified as variants of interest or variants of concern and were more closely related to the original SARS-CoV-2 strain. This study further indicates that the vaccine is effective against a wide range of variants in addition to the prototype strain.
It is important that this study includes the demographic diversity of the experimental population, and therefore it indicates the effectiveness of the vaccine among different races and ethnic minorities. Among the various demographic groups, the effectiveness of NVX-CoV2373 among the Latin American or Latino population in the United States was found to be lower compared to other demographic groups. This could be due to an unidentified host or viral factor. A similar finding has been reported for another COVID-19 vaccine; however, the reason behind this finding has not yet been addressed.
This study includes several limitations, for example, exclusion of participants in older age groups, and estimation of vaccine efficacy in this group therefore remained unknown. However, the UK phase included three clinical trials with NVX-CoV2373 participants over 65 years of age and reported vaccine efficacy of 88.9%, which is comparable to the estimates associated with younger age groups. Another limitation of this study is the disproportionate number of deblinding requests from trial participants in the early stages of the trial, which resulted in the exclusion of a large number of participants from the placebo control group.
Although the follow-up period was limited, ie. about three months, it had been in accordance with the desired period of emergency use permit. The overall efficacy of this vaccine has been reported to be high regardless of the circulating strain. However, the authors have proposed long-term safety, blinded crossover, and hazard models for future study to further validate the efficacy and safety of NVX-CoV2373.