Covid-19 vaccine developments across the globe

Second waves of Covid-19 will coincide with the arrival of winter in the northern hemisphere, highlighting a critical period in the timeline of the pandemic, and the development of a viable vaccine is imperative to prevent a worsening of its impact. Researchers worldwide are moving at a rapid pace to identify and develop viable vaccine candidates.

The largest proportion of vaccine trials are currently in planned status, with Phase I studies (42.7%) holding the largest proportion of trials. Phase II studies have the largest proportion of vaccine trials that are in ongoing status (15.1%), followed by Phase III (12.5%) and Phase I (7.9%). Almost all Phase IV Covid-19 vaccine trials utilise the BCG vaccine. At present, no Covid-19 vaccine clinical trials have been terminated.

Only 2.9% of Covid-19 vaccine trials have been completed, which highlights the importance of interim results being reported by sponsors to proceed to later stages of development. Where site locations are concerned, the US takes the lead (11.8%), narrowly outnumbering second-place China (11.0%) and third-place India (9.7%). There are no European countries within the top five, potentially suggesting a prioritisation of therapeutics ahead of vaccines.

In regard to vaccine targets, the spike protein (S-protein) is the most frequently utilised target site. This can be attributed to the surface of the Covid-19 molecule being covered with S-proteins, allowing it to attach to host cell receptors, leading to the viral entry into the host cell. This results in the fusion of the viral and host cell membrane causing the host cell to become infected; the prevention of the S-protein binding to the host cell may therefore prevent infection.

The US currently has a number of exciting vaccine prospects that are being developed. The lead US candidates are currently being developed by Moderna, Pfizer-BioNTech, Johnson & Johnson and Novavax.

Moderna’s mRNA-1273 serves as the first vaccine to undergo human trials and is one of the more promising prospects. mRNA-1273 introduces a messenger ribonucleic acid (mRNA) sequence into the body that encodes for the S-protein’s production, prompting the immune system to form an immune response against the S-protein.

Results from Moderna’s Phase I study demonstrate that the vaccine provides an immune response, producing a mean neutralising antibody titer that exceeds that of convalescent sera. Moderna has also recently published updated data from the Phase I trial, which show the vaccine produces a neutralising antibody response in elderly subjects, with a tolerable safety profile. The vaccine is currently in Phase III trials with efficacy data likely to be reported in November; nonetheless, the US government has already committed to buying 100 million doses.

The University of Oxford’s collaboration with AstraZeneca serves as one of the most promising prospects from Europe. The vaccine candidate AZD-1222 uses adenoviruses that have been genetically altered to prevent replication and include a replication-deficient chimpanzee adenovirus vector (ChAdOx1), which delivers the S-protein into the body to prompt an immune response.

Results from the Phase I/II study had shown the vaccine to produce a significant response leading to a four-fold increase in antibodies targeted against the S-protein as well as a T-cell response. With regards to the safety profile, the vaccine was also tolerated barring minor side effects such as headache and fatigue.

The vaccine progressed to a multinational Phase III trial across all adult age groups with a view to enroll 50,000 participants. However, on 8 September AstraZeneca placed the trial on temporary pause due to a potentially unexplained illness in one of the trial participants. Since then, a review of the safety data has been carried out by international regulators in the UK, India, Japan, South Africa and Brazil, all of which have deemed the study safe to resume. Nonetheless, the FDA is yet to approve the recommencement of the US arm of the study. Furthermore, increased transparency is required with regards to unexplained illness to ensure public trust is upheld, avoiding wide-scale vaccination distrust, which may hamper the battle against Covid-19.

In China, state-run Chinese pharmaceutical company Sinopharm is producing a vaccine in collaboration with the Wuhan Institute of Biological Products. Interim analysis of the Phase I and Phase II trials has shown the vaccine to demonstrate immunogenicity while also having an adequate safety profile. The Phase I and II studies were conducted in China’s Henan Province; however, the Phase III study was relocated to the United Arab Emirates (UAE). The sponsor selected this country due to population diversity; this may signify Sinopharm’s determination in gathering varied data in order to market the vaccine worldwide as soon as possible.

Interestingly, a report from the New Yorker has stated that hundreds of thousands of Chinese citizens have already been vaccinated with Sinopharm’s vaccine through an emergency use authorisation. The vaccination of such a large number of individuals prior to regulatory approval does raise concerns, as the full safety and efficacy profiles of the vaccine are not fully developed, though participation was voluntary.

In Russia, the research institution Gamaleya Federal Research Center of Epidemiology and Microbiology has produced a vaccine named Sputnik V, financed by the state-run Russian Direct Investment Fund. The vaccine utilises adenoviruses to present the S-protein into the body to elicit an immune response, and requires booster injections three weeks after the first dose to strengthen the immune response.

Phase I/II results have shown the vaccine to induce a strong immune response in all participants while displaying a tolerable safety profile. This led the Russian Ministry of Health to approve the vaccine, making Russia the first country to approve it. Nevertheless, the approval of a vaccine is typically dependent on Phase III trial data, which are not yet available, and therefore the approval of Sputnik V has been met with some skepticism.

While the induction of a strong immune response is promising, Phase III data would ultimately determine if the immune response translates into a sufficient level of immunity. The vaccine is currently in Phase III/IV trials, where further information regarding immunity should be established.

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