One Step Closer to an HIV Vaccine

In an ideal world, there would be a vaccine against the human immunodeficiency virus (HIV). An improved animal model developed by researchers from the Perelman School of Medicine at the University of Pennsylvania could one day make a vaccine a reality.

In an ideal world, there would be a vaccine against the human immunodeficiency virus (HIV). An improved animal model developed by researchers from the Perelman School of Medicine at the University of Pennsylvania could one day make a vaccine a reality.

There are vaccines to protect against viral diseases such as the flu, measles, and hepatitis B, so why has creating one for HIV been such a challenge? Vaccines work by introducing non-infectious components or a weakened form of a microbe to the immune system so that it can build up a defense against it. However, HIV mutates rapidly and its envelope is coated with derived sugars so the immune system does not view it as foreign. For nearly 30 years, researchers have been trying to find a way around these challenges in order to develop a vaccine.

The envelope of the virus is key, George M. Shaw, MD, PhD, Hui Li, MD, and colleagues explained in the study published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

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The Penn team created genetically engineered viruses with the HIV envelope but with simian immunodeficiency virus (SIV) viral components — called chimeric simian-human immunodeficiency viruses (SHIVs). HIV can’t infect rhesus macaques (monkeys), but SHIVs can and causes a disease similar to AIDS.

Out of 850 amino acids that make up the viral envelope, “Env375” is the one that really matters.

“We found that changing a single amino acid in the envelope coat protein of naturally occurring HIV strains led to dramatic differences in the ability of SHIVs to infect monkeys, while at the same time retaining the native-like features of the virus envelope and its interaction with the human immune system,” Shaw, a professor of Hematology/Oncology and Microbiology, said in a news release.

Based off of this discovery, the researchers created “designer SHIVs” and infected monkeys with it. Many of the animals’ host antibody response included the development of neutralizing antibodies — similar to what happens in humans when HIV is present. This finding means that researchers can observe the virus envelope in a controlled setting.

“Changing this one amino acid in HIV to resemble variants found in SIV enhanced the entry of SHIVs into monkey CD4 T cells by a thousand-fold. It was like night and day,” continued Li, a research assistant professor of Hematology/Oncology.

This research is far from over as the team plans to assess the HIV envelope’s molecular pathways as well as the corresponding neutralizing antibodies in humans and monkeys. The hope is that this will serve as a guide to finally developing an HIV vaccine.

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