Intrastructural Help: Harnessing T Helper Cells Induced by Licensed Vaccines for Improvement of HIV Env Antibody Responses to Virus-Like Particle Vaccines

Elsayed H, Nabi G, Mckinstry WJ, Khoo KK, Mak J, Salazar AM, Tenbusch M, Temchura V, Überla K (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Journal of Virology American Society for Microbiology

Book Volume: 92

Journal Issue: 14

DOI: 10.1128/JVI.00141-18

Abstract

Induction of persistent antibody responses by vaccination is generally thought to depend on efficient help by T follicular helper cells. Since the T helper cell response to HIV Env may not be optimal, we explored the possibility of improving the HIV Env antibody response to virus-like particle (VLP) vaccines by recruiting T helper cells induced by commonly used licensed vaccines to provide help for Env-specific B cells. B cells specific for the surface protein of a VLP can internalize the entire VLP and thus present peptides derived from the surface and core proteins on their major histocompatibility complex class II (MHC-II) molecules. This allows T helper cells specific for the core protein to provide intrastructural help for B cells recognizing the surface protein. Consistently, priming mice with an adjuvanted Gag protein vaccine enhanced the HIV Env antibody response to subsequent booster immunizations with HIV VLPs. To harness T helper cells induced by the licensed Tetanolpur vaccines, HIV VLPs that contained T helper cell epitopes of tetanus toxoid were generated. Tetanol-immunized mice raised stronger antibody responses to immunizations with VLPs containing tetanus toxoid T helper cell epitopes but not to VLPs lacking these epitopes. Depending on the priming immunization, the IgG subtype response to HIV Env after the VLP immunization could also be modified. Thus, harnessing T helper cells induced by other vaccines appears to be a promising approach to improve the HIV Env antibody response to VLP vaccines. IMPORTANCE Induction of HIV Env antibodies at sufficient levels with optimal Fc effector functions for durable protection remains a challenge. Efficient T cell help may be essential to induce such a desirable antibody response. Here, we provide proof of concept that T helper cells induced by a licensed vaccine can be harnessed to provide help for HIV Env-specific B cells and to modulate the Env-specific IgG subtype response.

Authors with CRIS profile

Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren Vladimir Temchura Institute of Clinical and Molecular Virology Klaus Überla Institute of Clinical and Molecular Virology

Involved external institutions

Oncovir, Inc. US United States (USA) (US) Commonwealth Scientific and Industrial Research Organisation (CSIRO) AU Australia (AU) Ruhr-Universität Bochum (RUB) DE Germany (DE) Deakin University AU Australia (AU)

How to cite

APA:

Elsayed, H., Nabi, G., Mckinstry, W.J., Khoo, K.K., Mak, J., Salazar, A.M.,... Überla, K. (2018). Intrastructural Help: Harnessing T Helper Cells Induced by Licensed Vaccines for Improvement of HIV Env Antibody Responses to Virus-Like Particle Vaccines. Journal of Virology, 92(14). https://doi.org/10.1128/JVI.00141-18

MLA:

Elsayed, Hassan, et al. "Intrastructural Help: Harnessing T Helper Cells Induced by Licensed Vaccines for Improvement of HIV Env Antibody Responses to Virus-Like Particle Vaccines." Journal of Virology 92.14 (2018).

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