Chronic schistosomiasis suppresses HIVspecific responses to DNA-MVA and MVAgp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model

Publication

https://doi.org/10.1371/journal.ppat.1007182

Domain

Fellow

PLoS Pathog 14(7): e1007182

Godfrey A. Dzhivhuho^1¤, Samantha A. Rehrl¹, Hlumani Ndlovu², William G. C. Horsnell^1,3,4,5, Frank Brombacher^1,3,6,7, Anna-Lise Williamson^1,3, Gerald K. Chege^1,7*

¹ Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, Western
Cape, South Africa,

² Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa,

³ Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa,
⁴ Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom,
⁵Laboratory of Molecular and Experimental Immunology and Neurogenetics, Centre Nationnal de la
Recherche Scientifique, University of Orleans and Le Studium Institute for Advanced Studies, Rue Dupanloup, Orléans, France,

⁶ International Centre for Genomic Engineering and Biotechnology - Cape Town Component, Cape Town, Western Cape, South Africa, 7 South African Medical Research Council, Cape Town, Western Cape, South Africa

¤ Current address: Department of Microbiology, Immunology and Cancer Biology, Myles H. Thaler Center for
AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, Virginia, United States of America.

* Gerald.Chege@mrc.ac.za

Abstract

Future HIV vaccines are expected to induce effective Th1 cell-mediated and Env-specific antibody responses that are necessary to offer protective immunity to HIV infection. However, HIV infections are highly prevalent in helminth endemic areas. Helminth infections induce polarised Th2 responses that may impair HIV vaccine-generated Th1 responses. In this study, we tested if Schistosoma mansoni (Sm) infection altered immune responses to SAAVI candidate HIV vaccines (DNA and MVA) and an HIV-1 gp140 Env protein vaccine (gp140) and whether parasite elimination by chemotherapy or the presence of Sm eggs (SmE) in the absence of active infection influenced the immunogenicity of these vaccines. In addition, we evaluated helminth-associated pathology in DNA and MVA vaccination groups. Mice were chronically infected with Sm and vaccinated with DNA+MVA in a prime+boost combination or MVA+gp140 in concurrent combination regimens. Some Sm-infected mice were treated with praziquantel (PZQ) prior to vaccinations. Other mice were inoculated with SmE before receiving vaccinations. Unvaccinated mice without Sm infection or SmE inoculation served as controls. HIV responses were evaluated in the blood and spleen while Smassociated pathology was evaluated in the livers. Sm-infected mice had significantly lower magnitudes of HIV-specific cellular responses after vaccination with DNA+MVA or MVA

Keywords

HIV vaccines

Enzyme-linked immunoassays

Vaccination and immunization

Antibodies

Immune response

T cells

Antibody response

Mouse models

Published by

Plos Pathogens