Vaccination detects latent HIV in laboratory studies

Vaccination with the SARS-CoV-2 mRNA vaccine showed that HIV hides in immune cells in the blood of people with HIV, according to lab research led by Weill Cornell Medicine investigators. The findings, published August 19 in Nature Communications, identify new tools for evaluating treatment approaches in development aimed at treating HIV.

there is prior knowledge of the influenza vaccine, for example, awakening of HIV and exposing it to the immune system; But it was not clear if this only occurs in influenza T cells, which is a known place where HIV hides.” Brad Jones, associate professor of immunology in medicine at Weill Cornell Medicine. “Our findings are exciting as we showed a stronger effect with the SARS-CoV-2 mRNA vaccine. It awakened HIV hiding in T cells in the blood of people who had not previously been exposed to the virus or 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 reproducing, lowering viral load in blood levels to help restore a healthy immune system and significantly reducing the risk of transmitting the virus to others. However, antiretroviral therapy does not cure HIV because some viruses that do not replicate effectively remain hidden in immune cells, which are called the latent reservoir of HIV. Scientists have been studying ways to get HIV out of the reservoir using latency-reversing agents until it is exposed to immune cells.

For their research, investigators, including co-authors Eva Stevenson, Sandra Terry and Dennis Cupertino, members of the Jones Laboratory, processed blood from unvaccinated HIV-infected individuals who had not previously had COVID-19 to Pfizer-BioNTech or Moderna. COVID-19 mRNA vaccine in test tubes. The Pfizer-BioNTech vaccine produced a greater release of HIV RNA.

Next, the researchers analyzed blood from individuals infected with HIV before the COVID-19 vaccination and after each of the two shots. 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 potent marker of recent attempts by CD8+ T cells to kill HIV. This response, observed after the first shot, was associated with a subsequent decrease in HIV RNA–suggesting some elimination of infected cells by enhanced CD8+ T cells.

Previous work by Jones and his team suggested that assessing responses in Nef-specific CD8+ T cells may be a more useful way to measure latency reversal compared to HIV RNA since the RNA may not ultimately convert into a protein that the immune system can recognize. . the system. The current study confirmed their hypothesis.

“Importantly, our lab studies found no evidence that exposing an infected person’s HIV reservoirs with an mRNA vaccine may pose a risk of transmission to others,” Jones said. “We did not observe any appreciable level of HIV RNA in the blood plasma after the vaccine augmentation and we expect that continued antiretroviral therapy will prevent any potential replication of HIV.”

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

“We plan to analyze Nef’s CD8+ T cells and look for granzyme B production as improved metrics for assessing latency reversal in clinical trials where the goal is to awaken HIV and expose it to the immune system, and hopefully other investigators will do that as well,” Jones said.

“It’s nice to see the development of an RNA vaccine completely imperfect,” he added. “Efforts to treat HIV in the 1990s using mRNA technology led to the development of current COVID-19 mRNA vaccines. Now, COVID-19 mRNA vaccines open a new door to HIV research.”

Jane Langel Freelance writer at Weill Cornell Medicine.

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