Divergent HIV-1-directed immune responses generated by systemic and mucosal immunization with replicating single-cycle adenoviruses in rhesus macaques

William E. Matchett, Stephanie S. Anguiano-Zarate, Pramod N. Nehete, Kathryn Shelton, Bharti P. Nehete, Guojun Yang, Stephanie Dorta-Estremera, Philip Barnette, Peng Xiao, Siddappa N. Byrareddy, Francois Villinger, Ann Hessell, Nancy Haigwood, K. Jagannadha Sastry, Michael A. Barry

    Research output: Contribution to journalArticle

    Abstract

    Most human immunodeficiency virus type 1 (HIV-1) infections begin at mucosal surfaces. Providing a barrier of protection at these may assist in combating the earliest events in infection. Systemic immunization by intramuscular (i.m.) injection can drive mucosal immune responses, but there are data suggesting that mucosal immunization can better educate these mucosal immune responses. To test this, rhesus macaques were immunized with replicating single-cycle adenovirus (SC-Ad) vaccines expressing clade B HIV-1 gp160 by the intranasal (i.n.) and i.m. routes to compare mucosal and systemic routes of vaccination. SC-Ad vaccines generated significant circulating antibody titers against Env after a single i.m. immunization. Switching the route of second immunization with the same SC-Ad serotype allowed a significant boost in these antibody levels. When these animals were boosted with envelope protein, envelope-binding antibodies were amplified 100-fold, but qualitatively different immune responses were generated. Animals immunized by only the i.m. route had high peripheral T follicular helper (pTfh) cell counts in blood but low Tfh cell counts in lymph nodes. Conversely, animals immunized by the i.n. route had high Tfh cell counts in lymph nodes but low pTfh cell counts in the blood. Animals immunized by only the i.m. route had lower antibody-dependent cellular cytotoxicity (ADCC) antibody activity, whereas animals immunized by the mucosal i.n. route had higher ADCC antibody activity. When these Env-immunized animals were challenged rectally with simian-human immunodeficiency virus (SHIV) strain SF162P3 (SHIV SF162P3 ), they all became infected. However, mucosally SC-Ad-immunized animals had lower viral loads in their gastrointestinal tracts. These data suggest that there may be benefits in educating the immune system at mucosal sites during HIV vaccination. IMPORTANCE HIV-1 infections usually start at a mucosal surface after sexual contact. Creating a barrier of protection at these mucosal sites may be a good strategy for to protect against HIV-1 infections. While HIV-1 enters at mucosa, most vaccines are not delivered here. Most are instead injected into the muscle, a site well distant and functionally different than mucosal tissues. This study tested if delivering HIV vaccines at mucosa or in the muscle makes a difference in the quality, quantity, and location of immune responses against the virus. These data suggest that there are indeed advantages to educating the immune system at mucosal sites with an HIV-1 vaccine.

    Original languageEnglish (US)
    Article numbere02016-18
    JournalJournal of virology
    Volume93
    Issue number10
    DOIs
    StatePublished - May 1 2019

    Fingerprint

    Adenoviridae
    Human immunodeficiency virus 1
    Macaca mulatta
    HIV-1
    Immunization
    immunization
    immune response
    antibodies
    Antibodies
    vaccines
    Adenovirus Vaccines
    Virus Diseases
    animals
    mucosal immunity
    Mucosal Immunity
    blood cell counts
    Mucous Membrane
    Blood Cell Count
    Helper-Inducer T-Lymphocytes
    infection

    Keywords

    • HIV-1
    • Mucosal
    • Prime-boost
    • Replicating
    • SHIV
    • Single-cycle adenovirus
    • Systemic

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

    Cite this

    Matchett, W. E., Anguiano-Zarate, S. S., Nehete, P. N., Shelton, K., Nehete, B. P., Yang, G., ... Barry, M. A. (2019). Divergent HIV-1-directed immune responses generated by systemic and mucosal immunization with replicating single-cycle adenoviruses in rhesus macaques. Journal of virology, 93(10), [e02016-18]. https://doi.org/10.1128/JVI.02016-18

    Divergent HIV-1-directed immune responses generated by systemic and mucosal immunization with replicating single-cycle adenoviruses in rhesus macaques. / Matchett, William E.; Anguiano-Zarate, Stephanie S.; Nehete, Pramod N.; Shelton, Kathryn; Nehete, Bharti P.; Yang, Guojun; Dorta-Estremera, Stephanie; Barnette, Philip; Xiao, Peng; Byrareddy, Siddappa N.; Villinger, Francois; Hessell, Ann; Haigwood, Nancy; Sastry, K. Jagannadha; Barry, Michael A.

    In: Journal of virology, Vol. 93, No. 10, e02016-18, 01.05.2019.

    Research output: Contribution to journalArticle

    Matchett, WE, Anguiano-Zarate, SS, Nehete, PN, Shelton, K, Nehete, BP, Yang, G, Dorta-Estremera, S, Barnette, P, Xiao, P, Byrareddy, SN, Villinger, F, Hessell, A, Haigwood, N, Sastry, KJ & Barry, MA 2019, 'Divergent HIV-1-directed immune responses generated by systemic and mucosal immunization with replicating single-cycle adenoviruses in rhesus macaques', Journal of virology, vol. 93, no. 10, e02016-18. https://doi.org/10.1128/JVI.02016-18
    Matchett, William E. ; Anguiano-Zarate, Stephanie S. ; Nehete, Pramod N. ; Shelton, Kathryn ; Nehete, Bharti P. ; Yang, Guojun ; Dorta-Estremera, Stephanie ; Barnette, Philip ; Xiao, Peng ; Byrareddy, Siddappa N. ; Villinger, Francois ; Hessell, Ann ; Haigwood, Nancy ; Sastry, K. Jagannadha ; Barry, Michael A. / Divergent HIV-1-directed immune responses generated by systemic and mucosal immunization with replicating single-cycle adenoviruses in rhesus macaques. In: Journal of virology. 2019 ; Vol. 93, No. 10.
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    AU - Anguiano-Zarate, Stephanie S.

    AU - Nehete, Pramod N.

    AU - Shelton, Kathryn

    AU - Nehete, Bharti P.

    AU - Yang, Guojun

    AU - Dorta-Estremera, Stephanie

    AU - Barnette, Philip

    AU - Xiao, Peng

    AU - Byrareddy, Siddappa N.

    AU - Villinger, Francois

    AU - Hessell, Ann

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