Human Papillomavirus Vaccine immune responses in an Olive baboon model is not compromised by chronic <i>Schistosoma mansoni</i> infections

Linda Obiero; Edinah Songoro; Martin Omondi; Ruth Nyakundi; Lucy Ochola; Linda Obiero; Edinah Songoro; Martin Omondi; Ruth Nyakundi; Lucy Ochola

doi:10.3934/microbiol.2025030

AIMS Microbiology

2025, Volume 11, Issue 3: 720-736. doi: 10.3934/microbiol.2025030

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Research article

Human Papillomavirus Vaccine immune responses in an Olive baboon model is not compromised by chronic Schistosoma mansoni infections

1.
Jomo Kenyatta University of Agriculture and Technology
2.
Kenya Institute of Primate Research

Received: 09 March 2025 Revised: 02 July 2025 Accepted: 15 July 2025 Published: 07 August 2025

Human papillomavirus (HPV) vaccines elicit specific serum antibodies that confer long-lasting protection and may reduce HPV-related cancers. However, helminthic infections such as chronic schistosomiasis infection at the time of HPV vaccination are known to alter immune responses. This study investigated the impact of chronic S. mansoni infection on immune responses to the HPV vaccine in olive baboons. Baboons were assigned to three groups: (1) untreated S. mansoni-infected, (2) S. mansoni-infected and treated with Praziquantel, and (3) uninfected controls. All received two doses of the Cervarix HPV vaccine four weeks apart. Immune responses were measured using flow cytometry and ELISA. Gardasil® quadrivalent HPV vaccine antigen was used in both ELISA and PBMC stimulation for cytokine ELISA supernatants. HPV-specific whole IgG levels significantly increased in all groups except for the untreated S. mansoni-infected group, whose increase was significant after the second dose. Similarly, IgG1 levels increased only after the second dose. There was no significant difference between the treated and untreated infected groups. These findings emphasize the importance of a booster dose for strong antibody production and suggest that a delayed HPV-specific whole IgG response in untreated S. mansoni-infected individuals reinforces the need for booster HPV vaccination in endemic regions. The results affirm the vaccine's effectiveness in S. mansoni endemic areas.
- Human papillomavirus,
- HPV vaccine,
- chronic schistosomiasis,
- innate immune cells,
- immune cells antibodies
Citation: Linda Obiero, Edinah Songoro, Martin Omondi, Ruth Nyakundi, Lucy Ochola. Human Papillomavirus Vaccine immune responses in an Olive baboon model is not compromised by chronic Schistosoma mansoni infections[J]. AIMS Microbiology, 2025, 11(3): 720-736. doi: 10.3934/microbiol.2025030

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Abstract

Human papillomavirus (HPV) vaccines elicit specific serum antibodies that confer long-lasting protection and may reduce HPV-related cancers. However, helminthic infections such as chronic schistosomiasis infection at the time of HPV vaccination are known to alter immune responses. This study investigated the impact of chronic S. mansoni infection on immune responses to the HPV vaccine in olive baboons. Baboons were assigned to three groups: (1) untreated S. mansoni-infected, (2) S. mansoni-infected and treated with Praziquantel, and (3) uninfected controls. All received two doses of the Cervarix HPV vaccine four weeks apart. Immune responses were measured using flow cytometry and ELISA. Gardasil® quadrivalent HPV vaccine antigen was used in both ELISA and PBMC stimulation for cytokine ELISA supernatants. HPV-specific whole IgG levels significantly increased in all groups except for the untreated S. mansoni-infected group, whose increase was significant after the second dose. Similarly, IgG1 levels increased only after the second dose. There was no significant difference between the treated and untreated infected groups. These findings emphasize the importance of a booster dose for strong antibody production and suggest that a delayed HPV-specific whole IgG response in untreated S. mansoni-infected individuals reinforces the need for booster HPV vaccination in endemic regions. The results affirm the vaccine's effectiveness in S. mansoni endemic areas.

Acknowledgments

This work was supported by The Department of Tropical and Infectious Disease (TID), of the Kenya Institute of Primate Research (KIPRE) and funded by Dr. Ruth Nyakundi and Dr. Lucy Ochola. We thank Prof. Abdussamad M. Abdussamad, Dr. Paul Ogongo, and Mr. Fred Nyundo, Mr. Sam Momanyi, Mr. Kevin Mugambi, Mr. Elisha Opiyo, and the entire Department of Tropical and Infectious Disease (TID), of the Kenya Institute of Primate Research (KIPRE). This research received no external funding.

Conflicts of interest

The authors declare no conflicts of interest.

Author contributions

Author Contributions: Conceptualization: L.O., R.N. and L.O.; Data curation, L.O., R.N. and L.O..; formal analysis, L.O., and R.N.; funding acquisition, R.N. and L.O.; investigation, L.O., M.O., R.N. and L.O.; methodology, L.O., M.O., R.N. and L.O.; project administration, R.N. and L.O.; supervision, R.N., E.S., and L.O.; Validation, R.N. and Lucy Ochola.; writing – original draft, L.O.; writing–review & editing, L.O., E.S., M.O., R.N., and L.O.

References

[1]	Cervical cancer. Available online: https://www.who.int/news-room/fact-sheets/detail/cervical-cancer (accessed on 12 February 2025)
[2]	Schuind AE, Balaji KA, Du A, et al. (2024) Human papillomavirus prophylactic vaccines: update on new vaccine development and implications for single-dose policy. JNCI Monographs 2024: 410-416. https://doi.org/10.1093/jncimonographs/lgae026
[3]	Mwenda V, Jalang'o R, Miano C, et al. (2023) Impact, cost-effectiveness, and budget implications of hpv vaccination in kenya: a modelling study. Vaccine 41: 4228-4238. https://doi.org/10.1016/j.vaccine.2023.05.019
[4]	Barnabas RV, Brown ER, Onono MA, et al. (2023) Durability of single-dose hpv vaccination in young Kenyan women: Randomized controlled trial 3-year results. Nat Med 29: 3224-3232,.
[5]	Stanley M (2010) HPV-immune response to infection and vaccination. Infect Agent Cancer 5: 19. https://doi.org/10.1186/1750-9378-5-19
[6]	Murthy KK, Salas MT, Carey KD, et al. (2006) Baboon as a nonhuman primate model for vaccine studies. Vaccine 24: 4622-4624. https://doi.org/10.1016/j.vaccine.2005.08.047
[7]	Magden ER, Nehete BP, Chitta S, et al. (2020) Comparative analysis of cellular immune responses in conventional and SPF Olive Baboons (Papio Anubis). Comp Med 70: 160-169. https://doi.org/10.30802/AALAS-CM-19-000035
[8]	Schwarz TF, Spaczynski M, Schneider A, et al. (2011) Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer vaccine in women aged 15–55 years. Hum Vaccin 7: 958-965. https://doi.org/10.4161/hv.7.9.15999
[9]	Kreimer AR, Struyf F, Del Rosario-Raymundo MR, et al. (2015) Efficacy of fewer than three doses of an HPV-16/18 AS04 adjuvanted vaccine: combined analysis of data from the costa rica vaccine trial and the PATRICIA trial. Lancet Oncol 16: 775-786. https://doi.org/10.1016/S1470-2045(15)00047-9
[10]	Malhotra I, McKibben M, Mungai P, et al. (2015) Effect of antenatal parasitic infections on anti-vaccine igg levels in children: a prospective birth cohort study in Kenya. PLoS Negl Trop Dis 9: e0003466. https://doi.org/10.1371/journal.pntd.0003466
[11]	Gent V, Waihenya R, Kamau L, et al. (2019) An Investigation into the Role of Chronic Schistosoma mansoni Infection on Human Papillomavirus (HPV) Vaccine Induced Protective Responses. PLoS Negl Trop Dis 13: e0007704. https://doi.org/10.1371/journal.pntd.0007704
[12]	Schuind AE, Balaji KA, Du A, et al. (2024) Human papillomavirus prophylactic vaccines: Update on new vaccine development and implications for single-dose policy. JNCI Monographs 2024: 410-416. https://doi.org/10.1093/jncimonographs/lgae026
[13]	Baisley K, Kemp TJ, Mugo NR, et al. (2024) Comparing one dose of HPV vaccine in girls aged 9–14 years in Tanzania (DoRIS) with one dose in young women aged 15–20 years in Kenya (KEN SHE): An immunobridging analysis of randomised controlled trials. Lancet Glob Health 12: e491-e499. https://doi.org/10.1016/S2214-109X(23)00586-7
[14]	CDCImpact of the HPV vaccine. Available from: https://www.cdc.gov/hpv/vaccination-impact/index.html
[15]	Nkurunungi G, Nassuuna J, Natukunda A, et al. (2024) The effect of intensive praziquantel administration on vaccine-specific responses among schoolchildren in Ugandan schistosomiasis-endemic islands (POPVAC A): An open-label, randomised controlled trial. The Lancet Global Health 12: e1826-e1837. https://doi.org/10.1016/S2214-109X(24)00280-8
[16]	Schistosomiasis (Bilharzia). Available from: https://www.who.int/health-topics/schistosomiasis
[17]	CDC Yellow BookSchistosomiasis (2024). Available from: https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/schistosomiasis
[18]	Dibo N, Liu X, Chang Y, et al. (2022) Pattern recognition receptor signaling and innate immune responses to schistosome infection. Front Cell Infect Microbiol 12. https://doi.org/10.3389/fcimb.2022.1040270
[19]	Souza COS, Gardinassi LG, Rodrigues V, et al. (2020) Monocyte and macrophage-mediated pathology and protective immunity during schistosomiasis. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.01973
[20]	Pearce EJ, MacDonald AS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2: 499-511. https://doi.org/10.1038/nri843
[21]	Gent V, Mogaka S (2018) Effect of helminth infections on the immunogenicity and efficacy of vaccines: A classical review. Am J Biomed Life Sci 6: 113-117.
[22]	Sabin EA, Araujo MI, Carvalho EM, et al. (1996) Impairment of tetanus toxoid-specific thl-like immune responses in humans infected with Schistosoma mansoni. J Infect Dis 173: 269-272. https://doi.org/10.1093/infdis/173.1.269
[23]	Elias D, Britton S, Aseffa A, et al. (2008) Poor immunogenicity of BCG in helminth infected population is associated with increased in Vitro TGF-β production. Vaccine 26: 3897-3902. https://doi.org/10.1016/j.vaccine.2008.04.083
[24]	Wajja A, Kizito D, Nassanga B, et al. (2017) The effect of current schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: an open-label trial. PLoS Negl Trop Dis 11: e0005440. https://doi.org/10.1371/journal.pntd.0005440
[25]	Musaigwa F, Kamdem SD, Mpotje T, et al. (2022) Schistosoma mansoni infection induces plasmablast and plasma cell death in the bone marrow and accelerates the decline of host vaccine responses. PLOS Pathogens 18: e1010327. https://doi.org/10.1371/journal.ppat.1010327
[26]	Natukunda A, Zirimenya L, Nassuuna J, et al. (2022) The effect of helminth infection on vaccine responses in humans and animal models: a systematic review and meta-analysis. Parasite Immunology 44: 1-10. https://doi.org/10.1111/pim.12939
[27]	Williamson AL (2023) Recent developments in human papillomavirus (HPV) vaccinology. Viruses 15: 1440. https://doi.org/10.3390/v15071440
[28]	Echevarria-Lima J, Moles R (2024) Monocyte and macrophage functions in oncogenic viral infections. Viruses 16: 1612. https://doi.org/10.3390/v16101612
[29]	Kapellos TS, Bonaguro L, Gemünd I, et al. (2019) Human monocyte subsets and phenotypes in major chronic inflammatory diseases. Front Immunol 10. https://doi.org/10.3389/fimmu.2019.02035
[30]	Pasmans H, Berkowska MA, Diks AM, et al. (2022) Characterization of the early cellular immune response induced by hpv vaccines. Front Immunol 13. https://doi.org/10.3389/fimmu.2022.863164
[31]	Ziegler-Heitbrock L, Ancuta P, Crowe S, et al. (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116: e74-80. https://doi.org/10.1182/blood-2010-02-258558
[32]	Thomas GD, Hamers AA, Nakao C, et al. (2017) Human blood monocyte subsets: a new gating strategy defined using cell surface markers identified by mass cytometry. Arterioscler Thromb Vasc Biol 37: 1548-1558. https://doi.org/10.1161/ATVBAHA.117.309145
[33]	Marimuthu R, Francis H, Dervish S, et al. (2018) Characterization of human monocyte subsets by whole blood flow cytometry analysis. J Vis Exp 57941. https://doi.org/10.3791/57941
[34]	Pasmans H, Berkowska MA, Diks AM, et al. (2022) Characterization of the early cellular immune response induced by HPV vaccines. Front Immunol 13. https://doi.org/10.3389/fimmu.2022.863164
[35]	Kervevan J, Chakrabarti LA (2021) Role of CD4+ T cells in the control of viral infections: recent advances and open questions. Int J Mol Sci 22: 523. https://doi.org/10.3390/ijms22020523
[36]	Snell LM, MacLeod BL, Law JC, et al. (2018) CD8+ T cell priming in established chronic viral infection preferentially directs differentiation of memory-like cells for sustained immunity. Immunity 49: 678-694.e5. https://doi.org/10.1016/j.immuni.2018.08.002
[37]	García-Piñeres A, Hildesheim A, Dodd L, et al. (2007) Cytokine and chemokine profiles following vaccination with human papillomavirus type 16 L1 virus-like particles. Clin Vaccine Immunol 14: 984-989. https://doi.org/10.1128/CVI.00090-07
[38]	Pinto LA Data from elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection (2023).
[39]	Gonçalves AK, Giraldo PC, Machado PRL, et al. (2015) Human Papillomavirus Vaccine-Induced Cytokine Messenger RNA Expression in Vaccinated Women. Viral Immunol 28: 339-342. https://doi.org/10.1089/vim.2015.0008

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