Invaplex Functions as an Intranasal Adjuvant for Subunit and DNA Vaccines Co-Delivered in the Nasal Cavity of Nonhuman Primates

Authors

Jeremy V. Camp, LSU Health Sciences Center- New Orleans
Robert L. Wilson, LSU Health Sciences Center- New OrleansFollow
Morgan Singletary, Tulane National Primate Research Center
James L. Blanchard, Tulane National Primate Research Center
Anna Aldovini, Children's Hospital Boston
Robert W. Kaminski, Walter Reed Army Institute of Research
Edwin V. Oaks, Walter Reed Army Institute of Research
Pamela A. Kozlowski, LSU Health Sciences Center- New OrleansFollow

Document Type

Article

Publication Date

8-1-2021

Publication Title

Vaccine: X

Abstract

Development of intranasal vaccines for HIV-1 and other mucosal pathogens has been hampered by the lack of adjuvants that can be given safely to humans. We have found that an intranasal Shigella vaccine (Invaplex) which is well tolerated in humans can also function as an adjuvant for intranasal protein and DNA vaccines in mice. To determine whether Invaplex could potentially adjuvant similar vaccines in humans, we simultaneously administered a simian immunodeficiency virus (SIV) envelope (Env) protein and DNA encoding simian-human immunodeficiency virus (SHIV) with or without Invaplex in the nasal cavity of female rhesus macaques. Animals were intranasally boosted with adenoviral vectors expressing SIV env or gag,pol to evaluate memory responses. Anti-SIV antibodies in sera and nasal, genital tract and rectal secretions were quantitated by ELISA. Intracellular cytokine staining was used to measure Th1-type T cells in blood. Macaques given DNA/protein immunizations with 0.5 mg Invaplex developed greater serum IgG, nasal IgA and cervicovaginal IgA responses to SIV Env and SHIV Gag,Pol proteins when compared to non-adjuvanted controls. Rectal IgA responses to Env were only briefly elevated and not observed to Gag,Pol. Invaplex increased frequencies of IFNγ-producing CD4 and CD8 T cells to the Env protein, but not T cell responses induced by the DNA. Ad-SIV boosting increased Env-specific polyfunctional T cells and Env- and Gag,Pol-specific antibodies in serum and all secretions. The data suggest that Invaplex could be highly effective as an adjuvant for intranasal protein vaccines in humans, especially those intended to prevent infections in the genital or respiratory tract.

First Page

1

Last Page

10

Volume

8

Publisher

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Camp, Jeremy V.; Wilson, Robert L.; Singletary, Morgan; Blanchard, James L.; Aldovini, Anna; Kaminski, Robert W.; Oaks, Edwin V.; and Kozlowski, Pamela A., "Invaplex Functions as an Intranasal Adjuvant for Subunit and DNA Vaccines Co-Delivered in the Nasal Cavity of Nonhuman Primates" (2021). School of Graduate Studies Faculty Publications. 24.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/24
10.1016/j.jvacx.2021.100105

File Format

pdf

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1872 KB