Research Article: Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model

Date Published: July 26, 2018

Publisher: Public Library of Science

Author(s): Godfrey A. Dzhivhuho, Samantha A. Rehrl, Hlumani Ndlovu, William G. C. Horsnell, Frank Brombacher, Anna-Lise Williamson, Gerald K. Chege, Guido Silvestri.

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

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 Sm-associated 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+gp140 compared to uninfected control mice. Similarly, gp140 Env-specific antibody responses were significantly lower in vaccinated Sm-infected mice compared to controls. Treatment with PZQ partially restored cellular but not humoral immune responses in vaccinated Sm-infected mice. Gp140 Env-specific antibody responses were attenuated in mice that were inoculated with SmE compared to controls. Lastly, Sm-infected mice that were vaccinated with DNA+MVA displayed exacerbated liver pathology as indicated by larger granulomas and increased hepatosplenomegaly when compared with unvaccinated Sm-infected mice. This study shows that chronic schistosomiasis attenuates both HIV-specific T-cell and antibody responses and parasite elimination by chemotherapy may partially restore cellular but not antibody immunity, with additional data suggesting that the presence of SmE retained in the tissues after antihelminthic therapy contributes to lack of full immune restoration. Our data further suggest that helminthiasis may compromise HIV vaccine safety. Overall, these findings suggested a potential negative impact on future HIV vaccinations by helminthiasis in endemic areas.

Partial Text

Human immunodeficiency virus (HIV) and parasitic helminthic worm infections are highly prevalent and geographically overlap each other in sub Saharan Africa (SSA) [1, 2]. A majority of inhabitants harbor at least one or more species of parasitic helminth infection [3–6] and an estimated 50% of the chronically infected individuals living in high-risk rural communities are co-infected with HIV [7]. Furthermore, re-infections after successful treatments are also very common in endemic areas. Therefore, it is very likely that successful future HIV vaccines will be administered to people who already have ongoing helminthiasis or have been previously infected and treated.

The present study investigated the impact of chronic schistosomiasis on the induction of T cell-mediated and antibody responses to candidate HIV vaccines in a mouse model, whether attenuation of vaccine responses can be reversed by pre-vaccination anti-helminthic treatment, and if vaccination with a T cell-based candidate vaccine has an adverse effect on helminth-associated pathology.

 

Source:

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