Journal Article

Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques

Verma, Anil, Iyer, Smita S, Shen, Xiaoying, Hawes, Chase E, Rajasundaram, Dhivyaa, Pedersen, Gabriel Kristian, Tomaras, Georgia D, Amara, Rama R, Elizaldi, Sonny R, Williams, LaTonya D, Smith, Justin C, Kozlowski, Pamela A

2024

Overview

CD4 T follicular helper cells (T fh ) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into T fh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the T fh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a T fh 1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and T fh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) T fh 1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC T fh 1 cells. While the generation of GC T fh 1/17 cells with CAF01 and GC T fh 1 cells with MPLA +QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml- MPLA; 5500; CAF01, 2155; p<0.05). Notably, interferon γ +Env-specific T fh responses were consistently higher with gp140 in MPLA +QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC T fh 1 induction promote persistent Env antibodies, important for protective immunity against HIV.

• Publisher: eLife Sciences Publications Ltd
• Subject: Adults / Antibodies / antibody persistence / Antibody response / Antigens / Boolean / CD4 antigen / Chemokines / Flow cytometry / Germinal centers / Glycoprotein gp160 / Helper cells / HIV / Human immunodeficiency virus / Humoral immunity / Immunity / Immunization / Immunoglobulin G / Interleukin 6 / IP-10 protein / Lipid A / Measles / Monophosphoryl lipid A / Proteins / Serology / T-dependent B cell response / vaccine efficacy / Vaccines / γ-Interferon