HIV envelope antigen valency on peptide nanofibers modulates antibody

A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial-based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofiber-based immunogens bearing the HIV gp120 envelope glycoprotein.

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Fig: Nanostructure and antigenicity of nanofiber-gp120 conjugates. (A) Schematic representation of gp120 antigens (maroon) covalently linked to fibrillizing peptides (blue). (B) TEM image of gp120 nanofibers stained with uranyl acetate. (C) Binding of antibodies against VRC01, B12, CH58, and CH22 epitopes to gp120 nanofibers prepared with different molar ratios of crosslinking agent SMCC, measured by ELISA. (D) Representation of gp120 antigenicity and loading density on nanofibers with selected formulation (10×) boxed in red. Antigenicity index for each condition was calculated by adding the AUC of ELISA binding curves from VRC01, B12, CH58 and CH22, then dividing by the sum AUC of unmodified gp120. (E) Dissociation rate constants (koff) of antibodies to gp120 and gp120 nanofibers measured by Biolayer Interferometry.

These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofibers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof-of-concept for a nanofiber vaccine platform generating broad, high binding antibody responses against the HIV-1 envelope glycoprotein.

Fries, C.N., Chen, JL., Dennis, M.L. et al. HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth. Sci Rep 11, 14494 (2021). https://doi.org/10.1038/s41598-021-93702-x

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