HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth

Abstract

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. 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.

Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation

“…This observation suggests an enhanced binding capacity induced by gp120-Q11 vaccination as compared to soluble gp120. Consistent with previous findings in mice ( 33 ), these results reinforce the importance of valency in enhancing antibody binding responses to HIV glycoprotein antigens.…”

“…In a recent study, we demonstrated that conjugating the HIV gp120 antigen to Q11 nanofibers induced antibody responses with stronger binding to heterologous HIV Envelope (Env) antigens than soluble gp120 in immunized mice and that enhancement of the antibody response was driven by the multivalent presentation of gp120 ( 33 ). Here, we immunized rabbits with Q11-conjugated gp120 (gp120-Q11) to evaluate the functional profile of vaccine-elicited antibodies.…”

Nanofiber Carriers of Therapeutic Load: Current Trends

“…Compared to subcutaneously delivered NFs, more resident T cells were produced providing faster response to influenza infection. Chemical plasticity enables customized display of antigens of self-assembling NFs, as demonstrated in the model HIV vaccine where folded glycoprotein antigen valency was associated with increased magnitude and breadth of immune response [ 151 ].…”

Use of Nanomaterials-based Enzymes in Vaccine Production and Immunization

“…Genetiс nаnо vассines have also played an influential role in the treatment of Ebola, HIV-1, аnd оrаl infeсtiоns [55,56]. DNA аnd RNA vассines are preferred to traditional vaccines owing to their simple purification and low production cost, however, their targeted delivery faces some constraints due to their specificity and stability [14,[57][58][59][60].…”