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

TitleSelf-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation.
Publication TypeJournal Article
Year of Publication2022
AuthorsChen J-L, Fries CN, Berendam SJ, Rodgers NS, Roe EF, Wu Y, Li SHang, Jain R, Watts B, Eudailey J, Barfield R, Chan C, M Moody A, Saunders KO, Pollara J, Permar SR, Collier JH, Fouda GG
JournalSci Adv
Volume8
Issue38
Paginationeabq0273
Date Published2022 Sep 23
ISSN2375-2548
KeywordsAIDS Vaccines, Animals, Glycosylation, HIV Antibodies, HIV Infections, HIV-1, Immunoglobulin Fc Fragments, Immunoglobulin G, Nanofibers, Vaccines, Subunit
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.

DOI10.1126/sciadv.abq0273
Alternate JournalSci Adv
PubMed ID36149967
PubMed Central IDPMC9506727
Grant ListP30 AI064518 / AI / NIAID NIH HHS / United States
R01 AI145016 / AI / NIAID NIH HHS / United States
T32 AI007392 / AI / NIAID NIH HHS / United States
T32 GM008555 / GM / NIGMS NIH HHS / United States