December 5, 2019

Rhesus macaques have long been considered the prime model for AIDS vaccine research because these monkeys’ immune systems are analogous to humans.

In fact, 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.

Now, 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.

This finding, supported by multiple NIH grants, comes from research at the University of Miami and the Wisconsin National Primate Research Center (WiNPRC). Lead researcher Mauricio Martins is an assistant professor working with long-time AIDS vaccine research experts and NPRC collaborators Ron Desrosiers and David Watkins in the Department of Pathology, Miller School of Medicine, University of Miami.

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.

Four out of 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 WiNPRC 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 genetically engineered strain, rRRV-SIVnfl, produced 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 virus 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, the authors say, 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 humans.

Photo credit: National Institute of Allergy and Infectious Diseases

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