Date: 07-Sep-2020

Preliminary Results From Russian Trials Find That Vaccine Candidates Led To No Serious Adverse Events And Elicit Antibody Response

Results from two early-phase Russian non-randomised vaccine trials (Sputnik V) in a total of 76 people are published today in The Lancet, finding that two formulations of a two-part vaccine have a good safety profile with no serious adverse events detected over 42 days, and induce antibody responses in all participants within 21 days.

Secondary outcomes (planned outcome measures that are not as important as the primary outcome measure, but are still of interest in evaluating the effect of an intervention [1]) from the trial also suggest the vaccines also produce a T cell response within 28 days.

The new paper reports the findings from two small phase 1/2 trials lasting 42 days - one studying a frozen formulation of the vaccine, and another involving a lyophilised (freeze-dried) formulation of the vaccine. 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 centigrade.

The two-part vaccine includes two adenovirus vectors - recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S) - which have been modified to express the SARS-CoV-2 spike protein. The adenoviruses are also weakened so that they cannot replicate in human cells and cannot cause disease (adenovirus usually causes the common cold).

These types of recombinant adenovirus vectors have been used for a long time, with safety confirmed in many clinical studies. Currently, several candidate COVID-19 vaccines using these vectors and targeting the SARS-CoV-2 spike protein have been tested in clinical trials [2]. These vaccines aim to stimulate both arms of the immune system - antibody and T cell responses - so they attack the virus when it is circulating in the body, and attack cells infected by SARS-CoV-2 [3].

Explaining why they are using two different adenovirus vectors, lead author Dr Denis Logunov, N F Gamaleya National Research Centre for Epidemiology and Microbiology, Russia, says: "When adenovirus vaccines enter people's cells, they deliver the SARS-CoV-2 spike protein genetic code, which causes cells to produce the spike protein. This helps teach the immune system to recognise and attack the SARS-CoV-2 virus. To form a powerful immune response against SARS-CoV-2, it is important that a booster vaccination is provided. However, booster vaccinations that use the same adenovirus vector might not produce an effective response, because the immune system may recognise and attack the vector. This would block the vaccine from entering people's cells and teaching the body to recognise and attack SARS-CoV-2. For our vaccine, we use two different adenovirus vectors in a bid to avoid the immune system becoming immune to the vector." [4]

The trials took place in two hospitals in Russia. The trials were open-label and non-randomised, meaning that participants knew that they were receiving the vaccine and were not assigned by chance to different treatment groups.

The trials involved healthy adults aged 18-60 years, who self-isolated as soon as they were registered for the trial and remained in hospital for the first 28 days of the trial (from when they were first vaccinated).

The frozen vaccine (Gam-COVID-Vac) was trialled in a branch of Burdenko Hospital, an agency of the Ministry of Defence, and involved both civilian and military volunteers. The freeze-dried vaccine (Gam-COVID-Vac-Lyo) took place at Sechenov University and all volunteers were civilians. All participants provided written informed consent.

In the phase 1 of each trial, participants received one component of the two-part vaccine on day 0 (four groups of nine participants were given the frozen or freeze-dried rAd26-S or rAd5-S component - see Figure 1). In the phase 2, which began no earlier than five days after the phase 1 trial began, participants received the full two-part vaccine (they received a prime vaccination with the rAd26-S component on day 0, followed by a booster vaccination with rAd5-S component on day 21. There were 20 participants each in the frozen and freeze-dried vaccine groups).