Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.

Amos, Joshua DWilks, Andrew BFouda, Genevieve GSmith, Shannon DColvin, LisaMahlokozera, TatendaHo, CarrieBeck, KristaOverman, R GlennDeMarco, C ToddHodge, Terry LLaBranche, Celia CMontefiori, David CDenny, Thomas NLiao, Hua-XinTomaras, Georgia DMoody, M AnthonyPermar, Sallie R2017-06-012017-06-012013-10https://hdl.handle.net/10161/14724The design of an effective vaccine to reduce the incidence of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breastfeeding will require identification of protective immune responses that block postnatal virus acquisition. Natural hosts of simian immunodeficiency virus (SIV) sustain nonpathogenic infection and rarely transmit the virus to their infants despite high milk virus RNA loads. This is in contrast to HIV-infected women and SIV-infected rhesus macaques (RhMs), nonnatural hosts which exhibit higher rates of postnatal virus transmission. In this study, we compared the systemic and mucosal B cell responses of lactating, SIV-infected African green monkeys (AGMs), a natural host species, to that of SIV-infected RhMs and HIV-infected women. AGMs did not demonstrate hypergammaglobulinemia or accumulate circulating memory B cells during chronic SIV infection. Moreover, the milk of SIV-infected AGMs contained higher proportions of naive B cells than RhMs. Interestingly, AGMs exhibited robust milk and plasma Env binding antibody responses that were one to two logs higher than those in RhMs and humans and demonstrated autologous neutralizing responses in milk at 1 year postinfection. Furthermore, the plasma and milk Env gp120-binding antibody responses were equivalent to or predominant over Env gp140-binding antibody responses in AGMs, in contrast to that in RhMs and humans. The strong gp120-specific, functional antibody responses in the milk of SIV-infected AGMs may contribute to the rarity of postnatal transmission observed in natural SIV hosts.AnimalsAntibodies, ViralB-LymphocytesCercopithecus aethiopsFemaleHIV InfectionsHumansMacaca mulattaMembrane GlycoproteinsMilk, HumanSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusViral Envelope ProteinsLack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.Journal article1098-5514