Researchers from the Emory Consortium for Innovative AIDS Research in Nonhuman Primates and their colleagues across North America have shown a new HIV vaccine is better at preventing infection and lasts longer, continuing to protect one year after vaccination. The findings, which are published online today in Nature Medicine, provide important insights for preventing HIV, and the timeliness of the results could also help shape the scientific community's approach to developing vaccines for COVID-19.
According to the researchers, the key to the new vaccine's markedly improved protection from viral infection is an alliance between neutralizing antibodies and cellular immunity. "Most efforts to develop an HIV vaccine focus on activating the immune system to make antibodies that can inactivate the virus, so called neutralizing antibodies," says Eric Hunter, PhD, professor of pathology and laboratory medicine at Emory, a researcher at the Emory Vaccine Center (EVC) and Yerkes National Primate Research Center, and a Georgia Research Alliance Eminent Scholar. "We designed our vaccine to also generate a strong cellular immune response that homed in on mucosal tissues so the two arms of the immune response could collaborate to give better protection," he continues.
Hunter is one of five senior authors of this study. Two of his Emory colleagues are also senior authors: Rama Amara, Ph.D., professor of microbiology and immunology at Emory and a researcher at Yerkes and the EVC; and Cynthia Derdeyn, Ph.D., professor of pathology and laboratory medicine at Emory and also an EVC and Yerkes researcher. The other senior authors are Bali Pulendran, Ph.D., a former EVC and Yerkes researcher who is now a professor at Stanford, and David Masopust, Ph.D., professor of microbiology and immunology at the University of Minnesota. The lead authors are Emory postdoctoral scholars Tysheena Charles, Ph.D., and Satish Bollimpelli, Ph.D., as well as postdoctoral scholars Prabhu Arunachalam, Ph.D., at Stanford, and Vineet Joag, Ph.D., at University of Minnesota. The research team also included members from Cornell University, Duke University, Louisiana State University and 3M Corp.
Some 38 million people worldwide live with AIDS. While antiviral medications limit the impact of the disease on daily life, HIV continues to infect 1.7 million people annually and cause some 770,000 deaths each year, which makes the Emory team's work a high priority.
In the new study, the researchers stimulated both serum and cellular immunity, which proved critical for the encouraging results. Working with rhesus macaques at Yerkes, the researchers inoculated three groups of 15 monkeys during a 40-week period. "Nonhuman primates remain the very best model for testing the potential of novel vaccines," says Hunter. The first group received several sequential inoculations of Env, a protein on the virus' outer surface known for stimulating antibody production, plus an adjuvant, a chemical combination often used in vaccines to enhance immune response. The second group was similarly inoculated but received additional injections of three different attenuated viruses modified to contain the gene for a HIV viral protein, Gag, that's known to stimulate cellular immunity. A third, control group, received injections containing only the adjuvant.
Following the 40-week regimen, all animals rested for 40 weeks, and then the researchers gave them booster shots of just the Env inoculation. After resting four more weeks, the researchers gave the animals 10 weekly exposures to SHIV, the simian version of HIV.
"Our results showed animals in the two experimental groups experienced significant initial protection from viral infection that was linked with high neutralizing antibody titers, particularly in the Env-only group," says Derdeyn. Even more notable, say the researchers, was several of the Env-plus-Gag animals, but none of the Env animals, remained uninfected even though they lacked robust levels of neutralizing antibodies. "This is an intriguing result because increasing the potency of neutralizing antibodies has been thought to be crucial to a vaccine's effectiveness, but doing so is difficult" Derdeyn adds.
Also difficult has been lengthening the duration of protection, but Amara says the current study shows promising results in addressing this.
When we rechallenged the study animals one year after giving the vaccines, the animals that received the Env-plus-Gag combination but not the Env-only vaccination showed a pronounced increase in the duration of protection. With these study results, we are one step closer to preventing HIV via a vaccine."
Rama Amara, Ph.D., professor of microbiology and immunology at Emory and a researcher at Yerkes and the EVC
The team will use the results to refine the way they approach vaccine development, including further assessing strategies to elicit cellular and neutralizing antibody responses for greater protection, with a goal of moving the new antibody plus T cell vaccine approach into clinical trials. "We think the same approach could be feasible for other pathogens, including influenza, TB, malaria and, now, COVID-19," he continues.
Arunachalam, P.S., et al. (2020) T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers. Nature Medicine. doi.org/10.1038/s41591-020-0858-8.