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

Abstract

To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) contribute to protection against several pathogens. In this study, we demonstrated that conjugation of HIV Envelope (Env) antigen gp120 to a self-assembling nanofiber material named Q11 induced antibodies with higher breadth and functionality when compared to soluble gp120. Immunization with Q11-conjugated gp120 vaccine (gp120-Q11) demonstrated higher tier 1 neutralization, ADCP, and ADCC as compared to soluble gp120. Moreover, Q11 conjugation altered the Fc N-glycosylation profile of antigen-specific antibodies, leading to a phenotype associated with increased ADCC in animals immunized with gp120-Q11. Thus, this nanomaterial vaccine strategy can enhance non-neutralizing antibody functions possibly through modulation of immunoglobulin G Fc N-glycosylation.

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

“…Recently, a nanomaterial-based HIV-1 vaccine was demonstrated to induce potent Fc effector functions correlating with unique antigen-specific antibody glycosylation ( 467 ). Q11—a frequently utilised vaccine nanomaterial—was conjugated to gp120, and co-administered with the Fc effector function enhancing adjuvant STR8S-C.…”

“…Q11—a frequently utilised vaccine nanomaterial—was conjugated to gp120, and co-administered with the Fc effector function enhancing adjuvant STR8S-C. This combination stimulated increased neutralisation and antibody breadth, as well as enhanced ADCC and, to a lesser degree, ADCP in rabbits ( 467 ). These enhancements to ADCC were correlated with changes in IgG Fc glycosylation patterns, including increased fucosylation and monogalactosylation of gp120-specific antibodies.…”

From antigen uptake to immune modulation: the multifaceted potential of peptide nanofibers as vaccine nanocarriers

“…Using fibrillised-β sheet-forming Q11-based peptide nanofibers conjugated to the HIV envelope-derived-antigen gp120, Chen et al illustrated the capacity of a single dose of the nanofiber vaccine to enhance the capacity of the induced antibodies to bind to the heterologous HIV envelope antigen in rabbits. 24…”

Adjuvant physiochemistry and advanced nanotechnology for vaccine development

“…For example, Fouda and colleagues conjugated the HIV envelop protein of gp120 to a nanofiber that was formed by self-assembling peptide Q11. 530 Rabbits immunized with Q11-gp120 induced antibodies with enhanced breadth and functionality than free forms of gp120. The conjugation modulated the Fc profile of antibodies, thereby increasing the non-neutralizing function of antibody-dependent cellular cytotoxicity.…”