Today, the Lancet, a leading medical journal, published the results of two open-label, non-random phase 1/2 clinical trials of the new crown vaccine developed by Russian scientists. The results showed that the vaccine showed good safety and tolerance, and effectively stimulated antibodies and cellular immune responses in adult volunteers.
Vaccine design based on two adenovirus vectors.
The vaccine uses a non-replicated recombinated adenovirus vector (rAd) to express the prickly protein (S protein) of the new coronavirus. Vaccine designs that use adenovirus vectors to express the new coronavirus S protein are currently being used in several new coronavirus vaccines, and are used in both Consino Biology and AstraZenecon-developed candidate vaccines that have entered Phase 3 clinical trials. One of the challenges of a vaccine based on adenovirus vector design is that the body’s immune system not only reacts immunely to the new coronavirus antigens expressed by the vector, but also to the antigens on the surface of the adenovirus as vectors. In fact, antibodies against adenovirus already exist in many people around the world.
To reduce the effect of the body’s immune response to adenovirus on vaccine effectiveness, the new coronary vaccine, called Gam-COVID-Vac, uses two different serotonin-type adenovirus vectors to express the S-protein of the new coronavirus. When vaccinated, the volunteers were vaccinated against adenovirus vectors based on serotype 26 (rAd26-S) and then received a second dose of the vaccine (rAd5-S) based on serotype 5 adenovirus vectors. This design and vaccination program can help reduce the effect of the body’s immune response to adenovirus antigens on vaccine effectiveness during a second vaccination.
The researchers also developed two new crown vaccine formulations, one for frozen and the other for freeze-dried powder, and tested the effectiveness of both vaccine formulations in clinical trials.
Drug Mingkang content team drawing.
Security of Gam-COVID-Vac.
The researchers conducted two open-label, non-random phase 1/2 clinical trials to test the effectiveness of frozen and freeze-dried powder vaccines, respectively.
In phase 1 clinical trials, volunteers received a dose of rAd26-S or rAd5-S vaccine intramuscular injections and were evaluated for safety over the next 28 days. In phase 2 clinical trials, volunteers were given the rAd5-S vaccine 21 days after receiving a dose of the rAd26-S vaccine and were evaluated for safety 42 days after the first injection.
Studies have shown that both the rAd26-S and rAd5-S vaccines show good safety. The study found no serious adverse events. The most common adverse reactions are redness, low fever, headache, weakness, muscle and joint pain at the injection site. These symptoms are similar to adverse reactions caused by other adenovirus vector-based vaccines previously reported.
Immunogenicity of Gam-COVID-Vac.
Antibody immune response.
The results showed that in Phase 2 clinical trials, 85 percent of the participants produced IgG antibodies for the new coronavirus S protein binding domain (RBD) 14 days after the first vaccination. After 21 days of vaccination, 100% of the participants produced RBD-specific antibodies. After receiving the second dose of rAd5-S vaccination, the participants’ RBD-specific antibody titration increased significantly.
Changes in RBD-specific IgG antibody titration after vaccination (Gam-COVID-Vac, frozen dosage form, Gam-COVID-Vac-Lyo, freeze-dried powder type)
The results of the meso-antibody test using the new human coronavirus showed that 100% of phase 2 trial participants produced meso-antibodies against the new coronavirus 42 days after the first vaccination, and that the level of the meso-antibody was similar to the average of patients recovering from COVID-19.
The change in antibody titration after vaccination (blue data points are the new crown vaccine for two different dosage forms).
Cellular immune response.
The researchers used three methods to detect vaccine-stimulated cellular immune responses: the proportion of new coronavirus-specific CD4-positive T-cells in the blood, the proportion of new coronary-specific CD8-positive T-cells, and the level of interferon-gamma (IFN-cym) released by exocytes (interferon-ting is one of the biomarkers of the type 1-assisted T-cell immune response). The results showed that gam-COVID-Vac’s two dosage forms significantly stimulated the growth of new coronavirus-specific CD4-positive and CD8-positive T cells, as well as the release of interferon-gamma. These results showed that Gam-COVID-Vac was effective in stimulating the participants’ cellular immune response.
Gam-COVID-Vac effectively stimulates the growth of CD4-positive T-cells (B) and CD8-positive T-cells (D) and the release of IFN-cym
The body’s immune response to adenovirus vectors.
Because the body’s immune response to adenovirus vectors may have an effect on the effectiveness of the new coronavirus, the researchers tested participants for the moderate antibody titration of recombinant adenovirus (rAd). The study found that, although the body produces a meso-antibody against recombinant adenovirus 28 days after the new coronavirus, there is no significant association between the resulting rAd and antibody titration and the participant-produced new coronavirus RBD antibody and the antibody titration, suggesting that the immune response to recombinant adenovirus did not have a significant effect on the effectiveness of the new coronavirus.
Furthermore, after being vaccinated against rAd26-S, the trial participants produced a moderate antibody against rAd26, but there was no significant increase in the moderate antibody titration against rAd5, which meant that the moderate antibody against rAd26d did not cross-react with rAd5 and may not hinder the effect of rAd5.
The participants had levels of meso-antibodies in the body for rAd after being vaccinated against Gam-COVID-Vac.
The Lancet also published comments by Professors Naor Bar-Zeev and Tom Inglesby of Johns Hopkins University in the United States. They say the study has several strengths, among which the development of freeze-dried powder forms means the vaccine can be stored and transported using cold-chain technology already available in the world. Its stability is important to ensure that vaccines can be distributed to remote areas to the maximum extent possible.
However, the review also noted that the study, like earlier studies of other vaccine candidates, had small sample sizes and short follow-up times. Moreover, the immunogenicity of the vaccine is not yet equivalent to the ability to protect against new coronavirus infections, and these characteristics still need to be validated in large Phase 3 clinical trials.
Moreover, since vaccination is for healthy populations, vaccine safety is critical, and current clinical trials have been unable to detect unusual or rare serious adverse events due to short follow-up times and low participation. Unlike clinical trials that test disease therapies, clinical trials that test vaccines need to consider a balance between the safety of the vaccine and the risk of infection, not the consequences of the disease. Unsafe vaccines can not only harm people who are vaccinated, but more importantly, undermine public confidence in vaccines and make them less likely to be vaccinated, thereby reducing their ability to protect against disease. As a result, vaccines in this study, like other candidates, ultimately need to prove their safety and ability in large-scale randomized clinical trials.