title: Mucosal immunization of lactating female rhesus monkeys with a transmitted/founder HIV-1 envelope induces strong Env-specific IgA antibody responses in breast milk.
abstract: 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.
authors.affiliation: Duke Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: Genevieve G A
authors.initials: GG
authors.lastname: Fouda
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Amos
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Wilks
authors.forename: Justin
authors.initials: J
authors.lastname: Pollara
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Ray
authors.forename: Anjali
authors.initials: A
authors.lastname: Chand
authors.forename: Erika L
authors.initials: EL
authors.lastname: Kunz
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Liebl
authors.forename: Kaylan
authors.initials: K
authors.lastname: Whitaker
authors.forename: Angela
authors.initials: A
authors.lastname: Carville
authors.forename: Shannon
authors.initials: S
authors.lastname: Smith
authors.forename: Lisa
authors.initials: L
authors.lastname: Colvin
authors.forename: David J
authors.initials: DJ
authors.lastname: Pickup
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
authors.forename: Glenn
authors.initials: G
authors.lastname: Overman
authors.forename: Krissey
authors.initials: K
authors.lastname: Eutsey-Lloyd
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Celia
authors.initials: C
authors.lastname: Labranche
authors.forename: Susan
authors.initials: S
authors.lastname: Barnett
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Sallie R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D058956:Administration, Mucosal; D000818:Animals; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D005260:Female; D015686:Gene Products, env / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000097:blood; D007774:Lactation / Q000276:immunology*; D008253:Macaca mulatta; D008895:Milk, Human / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015686:Gene Products, env; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA