Lack of B cell dysfunction is associated with functional, gp120-dominant antibody responses in breast milk of simian immunodeficiency virus-infected African green monkeys.
The 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.
Duke Human Vaccine Institute.
Joshua D
JD
Amos
Andrew B
AB
Wilks
Genevieve G
GG
Fouda
Shannon D
SD
Smith
Lisa
L
Colvin
Tatenda
T
Mahlokozera
Carrie
C
Ho
Krista
K
Beck
R Glenn
RG
Overman
C Todd
CT
DeMarco
Terry L
TL
Hodge
Celia C
CC
LaBranche
David C
DC
Montefiori
Thomas N
TN
Denny
Hua-Xin
HX
Liao
Georgia D
GD
Tomaras
M Anthony
MA
Moody
Sallie R
SR
Permar
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology; D006801:Humans; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology*; D008895:Milk, Human / Q000166:cytology* / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus