The unprecedented burden of the pandemic continues alongside new threats posed by Covid-19 variants circulating globally. Governments worldwide are ramping up vaccination programs with researchers moving at rapid pace to study viral variants and continue the development of viable vaccine candidates, the protective effects offered by the leading vaccines may be reduced by the fast-spreading variants. Continued research is imperative to prevent a worsening of the impact of Covid-19. This article examines the current landscape of vaccine clinical studies and worldwide developments.
As shown in Figure 1, the US takes the research lead, accounting for 11.5% of ongoing Covid-19 vaccine studies with China following with 7.6%, narrowly outnumbering India at 7.3%. Germany follows in fourth place with 4.6%; Brazil, the UK, and Australia are tied with 4.2% each.
The largest proportion of ongoing vaccine trials are now in Phase II (38.6%) and Phase III (36.3%), after Phase I studies dominated the earlier period of the pandemic. As clinical trials progress, more effectiveness results of vaccine candidates have become available. The first data released, for Moderna’s mRNA-1273 and Pfizer/BioNTech’s BNT162b2, displayed the highest efficacy levels of around 95%; these vaccines model the immune response around the spike protein. Consequently, 87.1% of vaccines in ongoing trials are now targeting the spike protein, demonstrating the high level of confidence obtained from the positive results of approved vaccine agents.
As shown in Table 1, BioNTech, Johnson and Johnson, and Gamaleya are the top three trial sponsors, each with five ongoing studies. Novavax, the University of Oxford, Sinovac, Moderna, Cadila, and CureVac are each sponsoring four studies. A number of the listed top sponsors have already attained some level of approval for their vaccines and are continuing research to expand on knowledge of the efficacy and safety profiles of these agents. This is especially important considering the emergence of new viral variants, as researchers need to ascertain whether the vaccines are as effective or if they require some level of modification to yield optimum immune response against the variants.
Focusing on the top sponsors without an approved vaccine, Johnson and Johnson is sponsoring the highest number of ongoing trials. J&J recently disclosed data from its UK Phase III study of its JNJ-78436735 vaccine, which met its primary endpoint by demonstrating 66% efficacy and a tolerable safety profile, and if approved, the vaccine will serve as the first single-dose vaccine.
Similarly, Novavax recently disclosed data from its UK Phase III study of its protein-based NVX-CoV2373 vaccine, which met its primary endpoint by demonstrating 89.3% efficacy and a tolerable safety profile. Even more encouraging, the vaccine was shown to demonstrate 85.6% efficacy against the UK variant strain however demonstrated a lower efficacy of 49.4% against the South African variant in a smaller study. NVX-CoV2373 is stable at fridge temperatures (2°C to 8°C), making it easier to transport and store.
Novavax initiated a rolling submission to the Medicines and Healthcare products Regulatory Agency (MHRA) in mid-January. Cadilia’s vaccine ZyCoV-D has proven to be well tolerated and to provide an immunogenic response in Phase I/II trials; ZyCoV-D recently entered Phase III studies involving approximately 30,000 participants. CureVac is developing a mRNA vaccine that moved into Phase III studies in December, and was shown to be well tolerated while producing an immune response; the vaccine was also shown to be suitable for standard fridge storage for at least three months.
This factor, alongside it being a mRNA vaccine like the Moderna and Pfizer/BioNTech vaccines with their superior effectiveness, have led to CureVac entering a collaboration and services agreement with Bayer in January 2021. This agreement provides substantial support from Bayer in the form of expertise and infrastructure in exchange for the potential to hold marketing authorization outside Europe.
With the global vaccine rollout progressing, it is imperative that clinical research continues at the same pace in order to constantly evolve the current knowledge in order to adapt to new challenges, such as new viral variants, and ultimately to produce a universal vaccine.