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

Anil Verma | Chase E Hawes | Sonny R Elizaldi | Justin C Smith | Dhivyaa Rajasundaram | Gabriel Kristian Pedersen | Xiaoying Shen | LaTonya D Williams | Georgia D Tomaras | Pamela A Kozlowski | Rama R Amara | Smita S Iyer
eLife | 2024

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 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 Tfh 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) Tfh1/17 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 Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 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 Tfh 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 Tfh1 induction promote persistent Env antibodies, important for protective immunity against HIV.

Pubmed ID: 38385642

Research resources used in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: HHSN272201800004C
  • Agency: NIAID NIH HHS, United States
    Id: U24 AI126683
  • Agency: NIH HHS, United States
    Id: P30 AI064518
  • Agency: NIH HHS, United States
    Id: K01 OD023034
  • Agency: NIH HHS, United States
    Id: R24 OD010976
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI150409
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI064518
  • Agency: NIH HHS, United States
    Id: HHSN272201800004C
  • Agency: NIH HHS, United States
    Id: R56AI150409

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