Health
Artificial immunogens show promise for inducing broadly neutralizing antibodies against HIV.
By combining cutting-edge immunology techniques, the researchers were able to stimulate the animals' immune systems and broadly induce a class of rare precursor B cells to HIV. Neutralizing antibodies The results of the study published today include: Nature ImmunologyThese are encouraging incremental steps toward developing a preventive HIV vaccine.
HIV is genetically diverse, making it difficult to target with a vaccine, but bNAbs may overcome this hurdle because they bind to parts of the virus that remain constant even as they mutate. Germline targeting is an immune system stimulation approach that induces naive (precursor) B cells to become mature B cells so that they can produce bNAbs. A class of bNAbs called 10E8 is a priority for HIV vaccine development, as it specifically neutralizes a broad range of HIV variants. 10E8 bNAbs are: Glycoproteins gp41, located on the surface of HIV, is involved in entry into human immune cells. Designing immunogens (molecules used in vaccines that induce specific immune system responses) to stimulate the production of 10E8 bNAbs has been challenging because key regions of gp41 are hidden in recessed crevices on the surface of HIV. No vaccine immunogen has generated bNAbs with the physical structure to reach and bind to gp41.
To address this challenge, the researchers designed immunogens on nanoparticles that mimic the appearance of specific parts of gp41. They inoculated rhesus macaques and mice with those immunogens and elicited specific responses from 10E8 B cell precursors, inducing antibodies that showed signs of maturing into bNAbs that could reach the hidden gp41 region. The researchers observed a similar response when they used mRNA-encoded nanoparticles in mice. They also found that the same immunogens generated B cells that could mature to produce another type of gp41-directed bNAb, called LN01. Finally, laboratory analysis of human blood samples showed that 10E8-class bNAb precursors naturally arise in people who are not infected with HIV, and that the immunogens bind to and isolate naive human B cells with 10E8-like characteristics. Together, these observations suggest that the promising immunological data from mice and macaques could be translated to humans.
The study was conducted by the Scripps HIV/AIDS Vaccine Development Consortium, one of two consortia supported by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH). The study also received support from collaborating partners, including the Bill & Melinda Gates Foundation and other NIH institutes and offices. According to the authors, these findings support the development of an immunogen as the first part of a multi-step vaccine regimen for humans. Their work further supports research into the development of a germline-targeted strategy to prime the immune system to elicit a bNAb, called VRC01. This bNAb was discovered by NIAID researchers about 15 years ago. The goal of this line of research is to develop an HIV vaccine that generates multiple classes of bNAbs to prevent HIV.
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Journal References:
Schiffner, T., et. (2024). Vaccination induces broadly neutralizing antibody precursors against HIV gp41. Nature Immunology. doi.org/10.1038/s41590-024-01833-w.
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