Vaccination exposes latent HIV in lab studies

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Vaccination with a SARS-CoV-2 mRNA vaccine revealed that HIV was hiding in immune cells in the blood of people living with HIV, according to laboratory research by Weill Cornell Medicine researchers. The findings, published Aug. 19 in Nature Communications, identify new tools for evaluating treatment approaches being developed aimed at curing HIV.

“There is prior knowledge of the flu vaccine, for example, waking up HIV and exposing it to the immune system; but it was unclear whether this occurs only in influenza-specific T cells, a known place where HIV hides,” said lead author Brad Jones, associate professor of immunology in medicine at Weill Cornell Medicine. “Our findings are exciting because we demonstrated a more potent effect with the SARS-CoV-2 mRNA vaccine. It awoke HIV that was hiding in the blood T cells of people who had never been exposed to the virus or the vaccine.

HIV attacks the body’s immune cells and tricks them into making copies of itself. Antiretroviral therapy (ART) turns HIV infection into a manageable chronic disease by preventing the virus from multiplying, lowering viral load in the blood to help restore a healthy immune system and significantly reduce the risk of HIV transmission. viruses to others. However, ART does not cure HIV because some viruses that do not actively multiply remain hidden in immune cells, called latent HIV reservoirs. Scientists have been studying ways to knock HIV out of the reservoir using latency-reversing agents so it can be exposed to immune cells.

For their research, the investigators, including co-first authors Eva Stevenson, Sandra Terry and Dennis Copertino, members of Jones’s lab, processed the blood of people living with HIV who were not vaccinated and had never had COVID-19 at Pfizer-BioNTech or Moderna COVID-19 mRNA vaccine in test tubes. The Pfizer-BioNTech vaccine produced greater release of HIV RNA.

Next, the researchers analyzed the blood of HIV-positive individuals before vaccination against COVID-19 and after each of the two vaccines. In particular, they found that killer CD8+ T cells that target cells marked with an early HIV gene product called Nef released the protein granzyme B, a robust marker of recent attempts by CD8+ T cells to kill HIV. This response, seen after the first shot, was correlated with a subsequent reduction in HIV RNA – suggesting some clearance of infected cells by boosted CD8+ T cells.

Previous work by Jones and his team has suggested that assessing responses in Nef-specific CD8+ T cells may be a more useful method for measuring latency reversal than HIV RNA, because the RNA might not ultimately be transformed into a protein that can be recognized by the immune system. system. The present study confirmed their hypothesis.

“Importantly, our laboratory studies found no evidence that exposure of HIV reservoirs in an infected individual using mRNA vaccination would pose a risk of transmission to others,” Jones said. “We observed no appreciable levels of HIV RNA in blood plasma after the vaccine booster and expect continued antiretroviral therapy to block any potential HIV replication.”

Jones and his lab validated their findings using anonymized blood samples provided by co-authors from Rockefeller University and Simon Fraser University in British Columbia, Canada.

“We plan to analyze Nef-specific CD8+ T cells and research granzyme B production as an improved measure to assess latency reversal in clinical trials where the goal is to arouse HIV and expose to the immune system, and hopefully other researchers will too,” Jones said.

“It’s nice to see the development of an mRNA vaccine coming full circle,” he added. “Efforts to cure HIV in the 1990s using mRNA technology led to the development of today’s COVID-19 mRNA vaccines. Now, COVID-19 mRNA vaccines open a new door for HIV research.

Jeanne Langille is a freelance writer for Weill Cornell Medicine.

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