Russia’s coronavirus vaccine is safe, elicits immune responses in Phase-1/2 trials

Russia’s Sputnik V vaccines for novel coronavirus have been found to be safe for a period of 42 days and capable of inducing antibody responses in all the 42 participants within 21 days. But the Phase-1/2 trials were open, not randomised, did not have a control group, and included totally 76 participants.

Russia’s Sputnik V vaccines for novel coronavirus have been found to be safe for a period of 42 days and capable of inducing antibody responses in all the 42 participants within 21 days. The trials were open and non-randomised and used two formulations — frozen and freeze-dried — of the vaccines on healthy adult volunteers. The trials did not use a placebo or control vaccine. The two vaccines use different adenoviral vectors (rAd26 and rAd5) for ferrying the full-length gene of coronavirus spike protein.

Safety of the two vaccines were assessed individually in the Phase-1 trial, while safety and immunogenicity were assessed in the Phase-2 trial by administering the vaccines as prime-boost. The results have been published in the journal The Lancet.

Both candidate vaccines were found to be safe and well tolerated. The most common adverse events were pain at injection site, hyperthermia, headache and muscle and joint pain. “Most adverse events were mild and no serious adverse events were detected,” they write. “In general, the adverse event profile did not differ from those reported in published work for other vector-based vaccines. The incidence of adverse events in our studies was slightly lower than in other work.”

The trial carried out between June 18 and August 3, enrolled 76 healthy adults; 38 were assigned to a group that received the frozen vaccine formulation and the remaining 38 were assigned to a group that received the freeze-dried vaccine formulation. During the Phase-1 trials, in the each of the two groups, nine participants received one dose of rAd26-S vaccine and another nine participants received one dose of rAd5-S vaccine. In the Phase-2 trials, 20 participants in each group received sequential injections of rAd26-S vaccine administered on day 0 and rAd5-S vaccine administered on day 21. The candidate vaccines were administered intramuscularly.

According to the paper, the vaccine produced both humoral and cellular immune responses. The IgG responses were elicited in all participants, with geometric mean titres “significantly” higher than those who have recovered from COVID-19. Specific T-cell responses (CD4 and CD8) peaked at day 28 after vaccination. Neutralising antibodies increased significantly at day 14 and continued to increase throughout the observation period. The titres of neutralising antibodies to SARS-CoV-2 were lower than those reported in studies of vaccines based on mRNA and ChAdOx1,” they write. But vaccination elicited the same level of neutralising antibodies compared with patients who have recovered from COVID-19.

All participants in the Phase-2 trials (40 participants) produced antibodies against the SARS-CoV-2 spike protein on day 42 of the trial.

In addition, neutralising antibody responses occurred in all 40 participants in the Phase-2 trials by day 42 whereas neutralising antibody responses were only found in 61% of participants in the Phase-1 study who only received rAd26-S (combined data for both the lyophilised and frozen vaccine formulations).

Comparing the antibody responses from the vaccination and from infection (using the convalescent plasma samples), the authors say that the antibody responses (at days 28 and 42) from vaccination appear to be higher than in people who have recovered from COVID-19. Vaccination also elicited the same level of SARS-CoV-2 neutralising antibodies as in people who had recovered from COVID-19.

T cell responses occurred in all participants in the phase 2 trials within 28 days of vaccination – including formation of T-helper (CD4) cells and T-killer (CD8) cells. The number of T-helper cells increased by 2.5% and the number of T-killer cells increased by 1.3% after vaccination with the frozen formulation, and by 1.3% and 1.1%, respectively, after vaccination with the freeze-dried formulation.

The frozen formulation is envisaged for large-scale use using existing global supply chains for vaccines, while the freeze-dried formulation was developed for hard-to-reach regions as it is more stable and can be stored at 2-8 degrees C.

According to the authors, the unpublished data of animal studies show “robust humoral and cellular immune responses were elicited in non-human primates, providing protection from SARS-CoV-2 infection”. They also write that the vaccine showed “100% protectivity in a lethal model of SARS-CoV-2 challenge in immunosuppressed hamsters”. No antibody-dependent enhancement of infection was seen in vaccinated animals.

Besides not being randomised and not using a control group, the duration of follow-up (42 days) was short. It included only male volunteers in some parts of phase 1, and had fewer number of participants (n=76). Although the trial was meant to recruit healthy volunteers aged 18–60 years, only fairly young volunteers were included (in their 20s and 30s, on average).