Update April 28, 2021: See also J Virol. 2021 Apr 28:JVI.00330-21.
By Jordana Lenon, Jan. 31, 2019
For the first time, scientists have used a genetically engineered herpesvirus to achieve significant vaccine protection against the AIDS virus in monkeys. Only live attenuated strains of simian immunodeficiency virus (SIV), the monkey version of HIV, have previously provided similar protection.
“Vaccine protection against SIVmac239 acquisition”, published Jan. 14 in the Proceedings of the National Academy of Sciences USA, is the result of a research collaboration by scientists at the University of Miami and the Wisconsin National Primate Research Center. First author on the paper Mauricio Martins is an assistant professor working with long-time nonhuman primate AIDS vaccine research experts Ron Desrosiers and David Watkins in the Department of Pathology, Miller School of Medicine, University of Miami. The other first author is Georg Bischof, a former research associate and graduate student in the Desrosiers lab who recently earned his Ph.D.
Martins earned his Ph.D. in cellular and molecular pathology at the University of Wisconsin-Madison in 2011, working in the Watkins lab here before relocating with the lab to Miami. Desrosiers, previously at Harvard, and Watkins have collaborated with the Wisconsin National Primate Research Center’s scientific and animal services staff for nearly 25 years.
Rhesus macaques have long been considered the prime model for AIDS vaccine research – as well as for understanding a host of other global infectious viruses such as Ebola, Zika, Dengue and malaria – because these monkeys’ immune systems are analogous to humans. Most medications approved to treat HIV in humans to date have resulted from biomedical research with macaques, much of it performed at the National Primate Research Centers.
Although several approaches to an AIDS vaccine show promise, molecularly cloned SIVmac239 is difficult for antibodies to neutralize, just as HIV-1 is in human infection, and a variety of approaches have had great difficulty achieving protective immunity against it, the authors reported.
“These latest results demonstrate for the first time significant protection against acquisition of SIVmac239 by any vaccine regimen other than live-attenuated SIV vaccines,” said Martins.
The modified herpesvirus vaccine regimen elicited lasting cellular immune responses to all nine SIV gene products tested, the researchers found.
“The monkeys vaccinated with this virus were protected against repeated intravenous SIV exposure, compared with non-vaccinated monkeys,” Desrosiers said.
Four out of the six vaccinated monkeys were protected against infection following repeated viral injections over four months, whereas five out of six control animals became infected over the same time span — and those five acquired it the most quickly of all the animals. Animal care and humane euthanasia were administered throughout this study by WNPRC veterinarians as needed and under the guidelines of the American Veterinary Medical Association.
The herpesvirus used in the study was rhesus monkey rhadinovirus (RRV). The recombinant strain, rRRV-SIVnfl, was engineered to produce not only replicating RRV, but noninfectious SIV, both working together to elicit a safe and strong enough response to fight off SIV infection. It is crucial for any prophylactic vaccine to recognize and kill all virion particles before they invade T-helper cells, take over their machinery and create more viruses. In AIDS, when those viruses eventually burst out, they kill their host cells, destroy the rest of the immune system and eliminate the body’s defenses against lethal opportunistic infections.
Further work is needed to define the critical components necessary for eliciting this protective immunity, evaluate the breadth of the protection against a variety of strains, and explore how this approach may be extended to human use, Desrosiers said.
The scientific, veterinary and animal care staff at the WNPRC who contributed to the study included Eva Rakasz, Kimberly Weisgrau, Nancy Schultz-Darken, Wendy Newton and Eric Alexander.
This project was supported by National Institutes of Health Grants R37 AI0639128 (to R.C.D.), K01 OD023032 (to M.A.M.), R37 AI052056 (to D.I.W.), and P01 AI094420 (to D.I.W.); by Wisconsin National Primate Research Center P51 Base Grant P51OD011106; and by federal funds from the National Cancer Institute under Contract HHSN261200800001E (to J.D.L.). The authors also acknowledge support from the Miami Center for AIDS Research at the University of Miami Miller School of Medicine funded by NIH Grant P30AI073961.