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Vaccine. 2019 Apr 17;37(17):2322-2330. doi: 10.1016/j.vaccine.2019.03.044. Epub 2019 Mar 27.

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

Author information

1
Infectious Diseases Division, University of Rochester Medical Center, Rochester, NY, United States.
2
Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY, United States.
3
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, United States.
4
Infectious Diseases Division, University of Rochester Medical Center, Rochester, NY, United States. Electronic address: james_kobie@urmc.rochester.edu.

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.

KEYWORDS:

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

PMID:
30926296
PMCID:
PMC6506229
[Available on 2020-04-17]
DOI:
10.1016/j.vaccine.2019.03.044
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