Multivalent antigen presentation increases the antibody binding breadth and neutralizing potency upon the immunization with a self-assembling HIV env vaccine

• Published in: Journal of the International AIDS Society 2021-01, Vol.24 (S1), p.45
• Main Authors: Fries, C, Dennis, M, Eudailey, J, Moody, A, Permar, S, Collier, J, Fouda, G
• Format: Article
• Language: English
• Subjects: AIDS (Disease); AIDS research; AIDS vaccines; Antigen-antibody reactions; Health aspects; Observations; Testing; Viral antigens
• ISSN: 1758-2652; 1758-2652
• DOI: 10.1002/jia2.25659

Background: Although previous studies have demonstrated that antigen valency is important to diversify the B cell repertoire, the ability of multivalent HIV vaccines to increase the breadth of vaccine-elicited antibodies and to promote neutralization remain unclear. Herein, we utilized a novel nanomaterial platform (Q11) to evaluate the influence of antigen valency on the HIV vaccine-elicited antibody responses. Methods: Self-assembly of the fiber-like nanoscale structure of Q11 was triggered by increasing the solvent ionic strength, followed by conjugation of HIV Envelope gycoprotein120 of clade C strains. We constructed vaccines with distinct valency by changing the concentration of antigen in the conjugation. Mice and rabbits were immunized with 15 [micro]g of gp120 or Q11-conjugated gp120 vaccine (gp120-Q11) along with a TLR7/8 and 9 agonist adjuvant STR8SC. A bead-based multiplex assay was used to measure antibody binding to heterologous Envs of subtypes B, C, and CRF_AE, and the TZM-bl cell assay was used to measure neutralization. Results: Mice immunized with gp120-Q11 demonstrated higher antibody titers against the autologous Env (p =0.027) after three immunizations; and higher binding to the 4 heterologous Env after each immunization than mice immunized with gp120 (Figure 1). The increased magnitude and breadth were only observed in mice immunized gp120-Q11 with 3 to 4 antigens on each fiber but not with gp120-Q11 with lower valency, suggesting that multivalent antigen presentation on Q11 contributed to the enhanced response. Immunization of rabbits indicated that Q11-gp120 also induced higher neutralization titer against the autologous tier 1 virus than gp120 (p =0.0285). Conclusions: We demonstrated that increasing the antigen valency by Q11 conjugation enhanced the humoral response in two distinct animal models, showing the potential of such nanomaterial in vaccine delivery. As a more clinically relevant model is required to further assess this platform, we plan to conjugate SOSIP trimer to Q11 and assess its immunogenicity in non-human primates.