Invaplex functions as an intranasal adjuvant for subunit and DNA vaccines co-delivered in the nasal cavity of nonhuman primates
| Autor: | Robert W. Kaminski, James Blanchard, Robert L. Wilson, Pamela A. Kozlowski, Anna Aldovini, Edwin V. Oaks, Morgan Singletary, Jeremy V. Camp |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Mucosal adjuvant
viruses medicine.medical_treatment T cell Respiratory tract medicine.disease_cause NS nasal secretions DNA vaccination Reproductive medicine CVS cervicovaginal secretions IM intramuscular NHP nonhuman primates Cytotoxic T cell Shigella vaccine Th T helper General Veterinary General Immunology and Microbiology biology business.industry Ad adenovirus Public Health Environmental and Occupational Health virus diseases RC581-607 Simian immunodeficiency virus Virology RS rectal secretions S-IgA secretory IgA Infectious Diseases medicine.anatomical_structure Regular paper Env envelope biology.protein HIV/AIDS Molecular Medicine Nasal administration Immunologic diseases. Allergy Antibody IN intranasal business Adjuvant IgA ICS intracellular cytokine staining |
| Zdroj: | Vaccine: X, Vol 8, Iss, Pp 100105-(2021) Vaccine: X |
| ISSN: | 2590-1362 |
| DOI: | 10.1016/j.jvacx.2021.100105 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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