A new study on HIV vaccines is striking in the latest issue of Nature Medicine, a sub-issue of Nature Medicine. Researchers from Stanford University School of Medicine and Emory University have teamed up to test the protective effects of a new HIV vaccine. Experiments in macaques have shown that the new vaccine produces a strong immune response that better protects against infection and provides lasting protection.
Not only does the findings provide important insights into THE prevention of AIDS, several study authors say, the findings are timely and have broad implications for developing vaccines against other pathogens, including the recent pandemic of the new coronavirus.
In their paper, the authors note that most of the current HIV vaccine development is focused on induced neutralizing antibody (nAb), which allows the immune system’s B cells to make more antibodies to inactivate the virus.
The team’s new vaccine strategy is to neutralize antibodies while strengthening cell immunity, which is to promote a stronger antiviral response to T-cells in the body, thereby enhancing the vaccine’s protective effect.
The study authors say that producing neutralizing antibodies and cellular immunity is like the immune system’s two arms, and if the cell immune response is strengthened, the combination of arms can provide better protection even if the level of neutralizing antibodies is not so high.
HIV-infected CD4-positive T-cells (Photo: NIAID)
To test the effectiveness of this “arms” vaccine, the researchers vaccinated and tested 45 macaques. “Inhuman primates are still the best model for testing the potential of new vaccines. Professor Eric Hunter, one of the study leaders, said.
The macaques were divided into three groups and received multiple injections over a 40-week period. The first group of vaccines consists of membrane proteins, the former proteins on the outer surface of HIV particles, which stimulate antibody production, the latter often used to enhance the immune response, and the second group adds an additional three modified viral vectors that are not infectious but contain genes that encode viral protein Gag to activate cell immunity, and the third group, which acts as a control and injects only azos. In week 80, the animals received a boost in immunization.
The experimental animals were divided into 3 groups, received different vaccination programmes, and received viral injections to test the protective effects of the different programmes (Photo Source: Resources 1)
From the 84th week after the first vaccination, the scientists exposed the animals to the virus for 10 weeks in a row with low doses of SHIV (ape HIV). Most of the animals in the control group were quickly infected, and the two experimental groups were significantly protected. Of these, 53% of the monkeys in the first group were uninfected;
The researchers noted that in the membrane protein vaccine group, high droplets of neutralizing antibodies are key to preventing infection. Interestingly, in the second group, some monkeys did not have high levels of neutralizing antibody titration, not meeting previously thought thresholds, while the animals were more protected.
“In the past, it has been thought that only increased neutralizing the efficacy of antibodies is the key to making vaccines more effective, and it has been very difficult to do so. Professor Cynthia Derdeyn, one of the study’s leaders, said. From the current results, the researchers’ desired “arms-” synergy has been effective in neutralizing the antibody.
Vaccination of the combined vaccine (blue line), the higher proportion of animals infected with the virus, and in infected animals, the viral load was generally one order of magnitude lower than in the control group (Photo: Resources 1)
Another challenge in developing an HIV vaccine is extending the vaccine’s protection, and the findings are also promising on the issue.
Nearly a year after the vaccination, scientists are once again using more SHIV to “poison” monkeys. The results showed that the combination of membrane protein-gag vaccine sedatium disenchanted two-thirds of the animals remained uninfected after repeated exposure to the virus, and the protective effect was more durable than receiving only the membrane protein vaccine.
After 8 months of enhanced immunity, the previously uninfected macaque son again has been exposed to the virus, and the combined vaccine (blue) still provides significant resistance to infection (Photo: Resources 1)
The study authors say the new vaccination program has improved its effectiveness, possibly because the vaccine induces a CD8-positive T-cell called “tissue resident memory T-cells.” These cells move to the site of the virus’s invasion (such as mucous membrane tissue) and stay there for a period of time to act as a sentinel. If the virus is seen again, these cells act immediately, secreting signals to other nearby immune cells to fight the virus at the site of infection.
“With these findings, we are one step closer to using vaccines to prevent AIDS,” said Dr. Rama Amara, a professor of microbiology and immunology at Emory University and co-lead in the study. “
The team said it will continue to refine the vaccine based on current results, including further evaluating strategies that can trigger cell response and neutralizing antibodies to provide stronger protection, with the ultimate goal of applying a new vaccine program for antibody-cell immunity to clinical trials. “We believe that the same approach is feasible for other pathogens, including influenza, tuberculosis, malaria and now the new coronavirus. Dr. Amara added at last.