The Lancet reports on the clinical results of phase 1/2 of Russia's new crown vaccine

On May 5, 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.
test results showed that the vaccine showed good safety and tolerance, and was effective in stimulating antibodies and cellular immune responses in adult volunteers.
a vaccine based on two adenovirus vectors that uses non-replicated recombinated adenovirus vectors (rAds) to express the prickly protein (S protein) of the new coronavirus.
vaccine design for the expression of the new coronavirus S protein using adenovirus vectors has been used in several new coronavirus vaccines, and has been developed by Consino Biology and AstraZenecon in 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.
, antibodies against adenovirus already exist in many people around the world.
to reduce the effects of the body's immune response to adenovirus on vaccine effectiveness, the new crown vaccine, called Gam-COVID-Vac, uses two different serum-type adenovirus vectors to express the S protein of the new coronavirus.
volunteers were vaccinated against a vaccine based on serotype 26 adenovirus vectors (rAd26-S) and then received a second dose of the vaccine (rAd5-S) based on serotype 5 adenovirus vectors, 21 days apart.
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.
researchers have developed two new crown vaccine formulations, one for frozen and the other for freeze-dried powder, and they have tested the effectiveness of both vaccine formulations in clinical trials.
Gam-COVID-Vac conducted two open-label, non-randomized Phase 1/2 clinical trials to test the effectiveness of frozen and freeze-dried powder vaccines, respectively.
phase 1 clinical trial, 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.
study found no serious adverse events.
most common adverse reactions were 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 in previous studies.
Gam-COVID-Vac immunoreactive immune response test results showed that in Phase 2 clinical trials, 85 percent of participants produced IgG antibodies against the new coronavirus S protein binding domain (RBD) 14 days after receiving the first vaccination.
21 days after vaccination, 100% of the participants produced RBD-specific antibodies.
a 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, photo source, reference. 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 the level of the meso-antibody was similar to the average of patients recovering from COVID-19.
and antibody titration changes after vaccination (blue data points are two different dosage forms of the new coronary vaccine, pictured: Reference 1) Cellular immune response researchers used three methods to detect vaccine-stimulated cellular immune response: new coronavirus-specific CD4 positive in the blood The proportion of T cells, the proportion of new coronary-specific CD8 positive T cells, and the interferon-γ (IFN-γ) level released by exoglobin monocytes (interferon-γ is one of the biomarkers of type 1 assisted T-cell immune response).
test 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-γ.
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-γ (F) (Photo Source: Reference: Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . the
study found that, although the body produces a meso-antibody against the 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, showing that the immune response to the recombinant adenovirus did not have a significant effect on the effectiveness of the new coronavirus.
More, although the trial participants produced a moderate antibody against rAd26 after being vaccinated against rAd26, there was no significant increase in the moderate antibody titration against rAd5, which meant that the mesothropoons against rAd26d did not cross-react with rAd5 and may not hinder the effect of rAd5.
test participants discussed the Lancet and published comments by Professors Naor Bar-Zeev and Tom Inglesby of Johns Hopkins University in the United States about the levels of mesotheliant antibodies in the body after being vaccinated with Gam-COVID-Vac (Photo Source: Reuters)
they say the study has several strengths, among other things, the development of freeze-dried powder forms means the vaccine can be stored and transported using cold chain technology that currently exists in the world.
its stability is important to ensure that vaccines are distributed to remote areas to the maximum extent possible.
, however, the review noted that the study, like earlier studies of other vaccine candidates, had small sample sizes and short follow-up times.
, 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.
also, because vaccines are given to 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 the balance between the safety of the vaccine and the risk of infection, not the consequences of the disease.
unsafe vaccines can not only harm the vaccinated population, but more importantly, undermine public confidence in the vaccine and make them reluctant to vaccinate, thereby reducing their ability to protect against disease.
, the vaccines in this study, like other candidates, ultimately need to prove their safety and ability in large-scale randomized clinical trials.
References: ( 1 ) Logunov et al., (2020). Safety and immunogenicity of an rAd26 and rAd5 vector-base heterologous prime-boost COVID-19 vaccine in two developments: two open, non-randomized phase 1/2 studies from Russia. The Lancet, Bar-Zeev and Inglesby (2020). COVID-19 vaccines: early success and remaining challenges. The Lancet, follow Medicinal Mingkang's WeChat Public No