Optimized Alum-Anchored HIV Env Immunogens

Technology

Like many vaccines, this composition utilizes adjuvants, in addition to the antigen, to elicit an immune response. Adjuvants are any substance that acts to augment or direct an immune response, typically working by recruiting immune cells to the site of vaccination and increasing the ability of immune cells to absorb invading pathogens. In this case, researchers used alum (aluminum hydroxide), which is among the most common and clinically safe adjuvants. This technology also uses an antigen derived from the surface of the HIV cell, although any antigen may be used. To promote antigen-alum binding with a strong binding affinity, a phosphoserine (pSer) tag is attached to the base of the immunogen molecule.

To further enhance the ability of the composition to fight HIV, researchers also incorporated aporous, cage-like nanoparticle as a co-adjuvant. In exemplary embodiments, this nanoparticle contains saponin, a plant-derived compound proven to be an effective adjuvant. This particle can optionally be bound to the alum or be co-administered with the initial composition.

To administer, an effective amount of the composition is given to the subject via injection, inhalation, or oral delivery to generate an enhanced immune response.

Problem Addressed

HIV/AIDS is one of the leading causes of death globally, with over 37 million people currently infected. Due to the diversity and high mutational capacity of the virus, there remains significant demand for an HIV vaccine for both treatment and prevention. This vaccine composition addresses this unmet need by leveraging the importance of timing antigen and adjuvant delivery to the lymph node, ensuring prolonged vaccine exposure and an enhanced immune response.

Advantages

• Increases immune cells' ability to generate antibodies that can neutralize up to all antigens in the system.
• Provides simple modification of immunogens with a short linker protein, leading to enhanced antibody and immune responses when combined with alum for extended vaccine dosing.
• Can involve any antigen deemed appropriate for intended use.

Publications

Moyer, T.J., Kato, Y., Abraham, W. et al. Engineered immunogen binding to alum adjuvant enhances humoral immunity. Nat Med 26, 430–440 (2020). https://doi.org/10.1038/s41591-020-0753-3

Rodrigues, K.A., Cottrell, C.A., Steichen, J.M., et al. Optimization of an alum-anchored clinical HIV vaccine candidate. npj Vaccines 8, 117 (2023). https://doi.org/10.1038/s41541-023-00711-0