Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Roshell Muir; Talibah Metcalf; Slim Fourati; Yannic Bartsch; Jacqueline Kyosiimire-Lugemwa; Glenda Canderan; Galit Alter; Enoch Muyanja; Brenda Okech; Teddy Namatovu; Irene Namara; Annemarie Namuniina; Ali Ssetaala; Juliet Mpendo; Annet Nanvubya; Paul Kato Kitandwe; Bernard S. Bagaya; Noah Kiwanuka; Jacent Nassuna; Victoria Menya Biribawa; Alison M. Elliott; Claudia J. de Dood; William Senyonga; Priscilla Balungi; Pontiano Kaleebu; Yunia Mayanja; Matthew Odongo; Jennifer Connors; Pat Fast; Matt A. Price; Paul L.A.M. Corstjens; Govert J. van Dam; Anatoli Kamali; Rafick Pierre Sekaly; Elias K. Haddad

doi:10.1371/journal.pntd.0011089

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Roshell Muir, Talibah Metcalf, Slim Fourati, Yannic Bartsch, Jacqueline Kyosiimire-Lugemwa, Glenda Canderan, Galit Alter, Enoch Muyanja, Brenda Okech, Teddy Namatovu, Irene Namara, Annemarie Namuniina, Ali Ssetaala, Juliet Mpendo, Annet Nanvubya, Paul Kato Kitandwe, Bernard S. Bagaya, Noah Kiwanuka, Jacent Nassuna, Victoria Menya BiribawaAlison M. Elliott, Claudia J. de Dood, William Senyonga, Priscilla Balungi, Pontiano Kaleebu, Yunia Mayanja, Matthew Odongo, Jennifer Connors, Pat Fast, Matt A. Price, Paul L.A.M. Corstjens, Govert J. van Dam, Anatoli Kamali, Rafick Pierre Sekaly, Elias K. Haddad^*

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vac-cines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vacci-nation serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4⁺ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower fre-quencies of circulating T follicular helper (cTfh) subpopulations pre-and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abro-gated vaccine responses in communities with endemic infections.

Original language	English (US)
Article number	e0011089
Journal	PLoS neglected tropical diseases
Volume	17
Issue number	7 July
DOIs	https://doi.org/10.1371/journal.pntd.0011089
State	Published - Jul 2023

Funding

We are grateful to the study participants, and healthcare and research staff from the Immunomodulation and Vaccines Programme and the Pathogen Genomics Phenotype and Immunity Programme at the MRC/UVRI and LSHTM Uganda Research Unit, the UVRIIAVI HIV Vaccine Program at the College of Health Sciences at Makerere University, Kampala-Uganda, and the International AIDS Vaccine initiative, for the invaluable contribution to this study.This work was supported by National Institutes of Health funding as part of the Human Immune Project Consortium (HIPC) to EKH and RPS #U19 AI128910 (https://www.nih.gov/). The SiVET study was supported by a grant from the United States Agency for International Development (USAID) [USAID reference number AID-OAA-A-16-00032] (https://www.usaid.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No authors received a salary from the funders.

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pntd.0011089

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Muir, R., Metcalf, T., Fourati, S., Bartsch, Y., Kyosiimire-Lugemwa, J., Canderan, G., Alter, G., Muyanja, E., Okech, B., Namatovu, T., Namara, I., Namuniina, A., Ssetaala, A., Mpendo, J., Nanvubya, A., Kitandwe, P. K., Bagaya, B. S., Kiwanuka, N., Nassuna, J., ... Haddad, E. K. (2023). Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses. PLoS neglected tropical diseases, 17(7 July), Article e0011089. https://doi.org/10.1371/journal.pntd.0011089

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title = "Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses",

abstract = "Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vac-cines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vacci-nation serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower fre-quencies of circulating T follicular helper (cTfh) subpopulations pre-and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abro-gated vaccine responses in communities with endemic infections.",

author = "Roshell Muir and Talibah Metcalf and Slim Fourati and Yannic Bartsch and Jacqueline Kyosiimire-Lugemwa and Glenda Canderan and Galit Alter and Enoch Muyanja and Brenda Okech and Teddy Namatovu and Irene Namara and Annemarie Namuniina and Ali Ssetaala and Juliet Mpendo and Annet Nanvubya and Kitandwe, {Paul Kato} and Bagaya, {Bernard S.} and Noah Kiwanuka and Jacent Nassuna and Biribawa, {Victoria Menya} and Elliott, {Alison M.} and {de Dood}, {Claudia J.} and William Senyonga and Priscilla Balungi and Pontiano Kaleebu and Yunia Mayanja and Matthew Odongo and Jennifer Connors and Pat Fast and Price, {Matt A.} and Corstjens, {Paul L.A.M.} and {van Dam}, {Govert J.} and Anatoli Kamali and Sekaly, {Rafick Pierre} and Haddad, {Elias K.}",

note = "Publisher Copyright: {\textcopyright} 2023 Muir et al.",

year = "2023",

month = jul,

doi = "10.1371/journal.pntd.0011089",

language = "English (US)",

volume = "17",

journal = "PLoS neglected tropical diseases",

issn = "1935-2727",

publisher = "Public Library of Science",

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Muir, R, Metcalf, T, Fourati, S, Bartsch, Y, Kyosiimire-Lugemwa, J, Canderan, G, Alter, G, Muyanja, E, Okech, B, Namatovu, T, Namara, I, Namuniina, A, Ssetaala, A, Mpendo, J, Nanvubya, A, Kitandwe, PK, Bagaya, BS, Kiwanuka, N, Nassuna, J, Biribawa, VM, Elliott, AM, de Dood, CJ, Senyonga, W, Balungi, P, Kaleebu, P, Mayanja, Y, Odongo, M, Connors, J, Fast, P, Price, MA, Corstjens, PLAM, van Dam, GJ, Kamali, A, Sekaly, RP & Haddad, EK 2023, 'Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses', PLoS neglected tropical diseases, vol. 17, no. 7 July, e0011089. https://doi.org/10.1371/journal.pntd.0011089

TY - JOUR

T1 - Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

AU - Muir, Roshell

AU - Metcalf, Talibah

AU - Fourati, Slim

AU - Bartsch, Yannic

AU - Kyosiimire-Lugemwa, Jacqueline

AU - Canderan, Glenda

AU - Alter, Galit

AU - Muyanja, Enoch

AU - Okech, Brenda

AU - Namatovu, Teddy

AU - Namara, Irene

AU - Namuniina, Annemarie

AU - Ssetaala, Ali

AU - Mpendo, Juliet

AU - Nanvubya, Annet

AU - Kitandwe, Paul Kato

AU - Bagaya, Bernard S.

AU - Kiwanuka, Noah

AU - Nassuna, Jacent

AU - Biribawa, Victoria Menya

AU - Elliott, Alison M.

AU - de Dood, Claudia J.

AU - Senyonga, William

AU - Balungi, Priscilla

AU - Kaleebu, Pontiano

AU - Mayanja, Yunia

AU - Odongo, Matthew

AU - Connors, Jennifer

AU - Fast, Pat

AU - Price, Matt A.

AU - Corstjens, Paul L.A.M.

AU - van Dam, Govert J.

AU - Kamali, Anatoli

AU - Sekaly, Rafick Pierre

AU - Haddad, Elias K.

PY - 2023/7

Y1 - 2023/7

N2 - Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vac-cines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vacci-nation serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower fre-quencies of circulating T follicular helper (cTfh) subpopulations pre-and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abro-gated vaccine responses in communities with endemic infections.

AB - Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vac-cines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vacci-nation serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower fre-quencies of circulating T follicular helper (cTfh) subpopulations pre-and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abro-gated vaccine responses in communities with endemic infections.

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JO - PLoS neglected tropical diseases

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Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Abstract

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ASJC Scopus subject areas

UN SDGs

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