New Vaccine Concept Induces Immune Responses for Multiple HIV Neutralizing Antibodies

In a significant advancement towards the creation of an HIV vaccine, researchers have employed advanced immunological techniques to successfully stimulate animals' immune systems to produce precursor B cells for a specific type of HIV broadly neutralizing antibodies (bNAbs). These findings represent a promising step towards developing a preventive HIV vaccine.

HIV presents unique challenges for vaccine development due to its genetic diversity. However, bNAbs offer hope because they target virus regions that remain stable even as the virus mutates. This study focuses on a bNAb known as 10E8, which is significant for HIV vaccine development because it neutralizes a wide variety of HIV strains. The 10E8 bNAb targets a conserved area of the glycoprotein gp41 on the surface of HIV, which is critical for the virus's entry into human immune cells. Creating an immunogen— a molecule that triggers a specific immune response— to stimulate 10E8 bNAbs has been difficult because this crucial gp41 region is hidden within a recessed area on the virus's surface. Previous vaccine immunogens failed to generate bNAbs capable of reaching and binding to gp41.

To overcome this obstacle, the researchers engineered immunogens on nanoparticles designed to mimic a specific part of gp41. They then vaccinated rhesus macaque monkeys and mice with these immunogens, which successfully elicited responses from the 10E8 B cell precursors. These precursor cells began to produce antibodies showing signs of maturing into bNAbs capable of targeting the hidden gp41 region. Similar responses were noted when using mRNA-encoded nanoparticles in mice. Additionally, the researchers found that these immunogens also produced B cells that could mature into another type of gp41-targeting bNAb known as LN01. Laboratory analyses of human blood samples revealed that precursor cells for 10E8 bNAbs naturally occur in people without HIV and that the immunogens could bind to and isolate these naïve human B cells with 10E8-like characteristics. These observations suggest that the promising results in mice and monkeys could potentially be replicated in humans.

The research was carried out by the Scripps Consortium for HIV/AIDS Vaccine Development, with support from the National Institutes of Health's (NIH) National Institute of Allergy and Infectious Diseases (NIAID), the Bill & Melinda Gates Foundation, and other NIH institutes and offices. The researchers indicate that these findings support the development of these immunogens as the initial part of a multi-step vaccine regimen for humans. Their work also supports ongoing research into a germline-targeting strategy designed to prime the immune system to produce a bNAb known as VRC01, which NIAID researchers discovered nearly 15 years ago. The ultimate goal of this research is to develop an HIV vaccine that can generate multiple classes of bNAbs to provide comprehensive protection against HIV.