Mucosal Immunization of Lactating Female Rhesus Monkeys with a Transmitted/Founder HIV-1 Envelope Induces Strong Env-Specific IgA Antibody Responses in Breast Milk
| Autor: | Celia C. LaBranche, Glenn Overman, Caroline A. Ray, Andrew B. Wilks, Justin Pollara, Susan W. Barnett, Guido Ferrari, Herman F. Staats, Haiyan Chen, Robert Parks, Sallie R. Permar, Norman L. Letvin, Lisa Colvin, Erika L. Kunz, Brooke E. Liebl, David C. Montefiori, Shannon D. Smith, Angela Carville, Krissey Eutsey-Lloyd, Hua-Xin Liao, Anjali Chand, Kaylan Whitaker, Georgia D. Tomaras, Joshua D. Amos, David J. Pickup, Genevieve G. Fouda, Barton F. Haynes |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Immunoglobulin A
viruses Immunology Immunization Secondary Vaccinia virus Breast milk Microbiology complex mixtures Immunoglobulin G Cell Line chemistry.chemical_compound Antibody Specificity Virology Vaccines and Antiviral Agents Vaccines DNA Administration Mucosal Animals Humans Lactation HIV vaccine Antibody-dependent cell-mediated cytotoxicity AIDS Vaccines biology Milk Human Antibody-Dependent Cell Cytotoxicity virus diseases Gene Products env Macaca mulatta Vaccination chemistry Insect Science biology.protein HIV-1 Female Immunization Vaccinia Antibody |
| Popis: | We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody responses in milk, hormone-induced lactating rhesus monkeys were vaccinated with a transmitted/founder (T/F) HIV Env immunogen in a prime-boost strategy modeled after the moderately protective RV144 HIV vaccine. Lactating rhesus monkeys were intramuscularly primed with either recombinant DNA ( n = 4) or modified vaccinia virus Ankara (MVA) poxvirus vector ( n = 4) expressing the T/F HIV Env C.1086 and then boosted twice intramuscularly with C.1086 gp120 and the adjuvant MF59. The vaccines induced Env-binding IgG and IgA as well as neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses in plasma and milk of most vaccinated animals. Importantly, plasma neutralization titers against clade C HIV variants MW965 ( P = 0.03) and CAP45 ( P = 0.04) were significantly higher in MVA-primed than in DNA-primed animals. The superior systemic prime-boost regimen was then compared to a mucosal-boost regimen, in which animals were boosted twice intranasally with C.1086 gp120 and the TLR 7/8 agonist R848 following the same systemic prime. While the systemic and mucosal vaccine regimens elicited comparable levels of Env-binding IgG antibodies, mucosal immunization induced significantly stronger Env-binding IgA responses in milk ( P = 0.03). However, the mucosal regimen was not as potent at inducing functional IgG responses. This study shows that systemic MVA prime followed by either intranasal or systemic protein boosts can elicit strong humoral responses in breast milk and may be a useful strategy to interrupt postnatal HIV-1 transmission. |
| Databáze: | OpenAIRE |
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