IL-33 enhances the kinetics and quality of the antibody response to a DNA and protein-based HIV-1 Env vaccine

Sanghita Sarkar, Michael S. Piepenbrink, Madhubanti Basu, Juilee Thakar, Michael C. Keefer, Ann Hessell, Nancy Haigwood, James J. Kobie

    Research output: Contribution to journalArticle

    Abstract

    Induction of a sustained and broad antibody (Ab) response is a major goal in developing a protective HIV-1 vaccine. DNA priming alone shows reduced levels of immunogenicity; however, when combined with protein boosting is an attractive vaccination strategy for induction of humoral responses. Using the VC10014 DNA and protein-based vaccine consisting of HIV-1 envelope (Env) gp160 plasmids and trimeric gp140 proteins derived from an HIV-1 clade B infected subject who developed broadly neutralizing serum Abs, and which has been previously demonstrated to induce Tier 2 heterologous neutralizing Abs in rhesus macaques, we evaluated whether MPLA and IL-33 when administered during the DNA priming phase enhances the humoral response in mice. The addition of IL-33 during the gp160 DNA priming phase resulted in high titer gp120-specific plasma IgG after the first immunization. The IL-33 treated mice had higher plasma IgG Ab avidity, breadth, and durability after DNA and protein co-immunization with alum adjuvant as compared to MPLA and alum only treated mice. IL-33 was also associated with a significant IgM Env-specific response and expansion of peritoneal and splenic B-1b B cells. These results indicate that DNA priming in the presence of exogenous IL-33 qualitatively alters the HIV-1 Env-specific humoral response, improving the kinetics and breadth of potentially protective Ab.

    Original languageEnglish (US)
    Pages (from-to)2322-2330
    Number of pages9
    JournalVaccine
    Volume37
    Issue number17
    DOIs
    StatePublished - Apr 17 2019

    Fingerprint

    Human immunodeficiency virus 1
    Antibody Formation
    HIV-1
    Vaccines
    vaccines
    kinetics
    antibodies
    DNA
    humoral immunity
    Proteins
    alum
    proteins
    neutralization
    Immunization
    mice
    immunization
    Immunoglobulin G
    AIDS Vaccines
    Antibody Affinity
    durability

    Keywords

    • Antibody
    • Envelope
    • HIV-1
    • IgM
    • IL-33
    • Vaccine

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

    Cite this

    Sarkar, S., Piepenbrink, M. S., Basu, M., Thakar, J., Keefer, M. C., Hessell, A., ... Kobie, J. J. (2019). IL-33 enhances the kinetics and quality of the antibody response to a DNA and protein-based HIV-1 Env vaccine. Vaccine, 37(17), 2322-2330. https://doi.org/10.1016/j.vaccine.2019.03.044

    IL-33 enhances the kinetics and quality of the antibody response to a DNA and protein-based HIV-1 Env vaccine. / Sarkar, Sanghita; Piepenbrink, Michael S.; Basu, Madhubanti; Thakar, Juilee; Keefer, Michael C.; Hessell, Ann; Haigwood, Nancy; Kobie, James J.

    In: Vaccine, Vol. 37, No. 17, 17.04.2019, p. 2322-2330.

    Research output: Contribution to journalArticle

    Sarkar, Sanghita ; Piepenbrink, Michael S. ; Basu, Madhubanti ; Thakar, Juilee ; Keefer, Michael C. ; Hessell, Ann ; Haigwood, Nancy ; Kobie, James J. / IL-33 enhances the kinetics and quality of the antibody response to a DNA and protein-based HIV-1 Env vaccine. In: Vaccine. 2019 ; Vol. 37, No. 17. pp. 2322-2330.
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