Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda.
OBJECTIVE
Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk.


METHODS
We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR.


RESULTS
Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n = 5), not IgA, diminished neutralization (mean 78 ± 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D.


CONCLUSIONS
Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.
Mucosal and Vaccine Research Colorado (MAVRC), University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Denver Veterans Affairs Medical Center, Denver, CO 80220, USA.
Jana M
JM
Palaia
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Michelle
M
McConnell
Mucosal and Vaccine Research Colorado (MAVRC), University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jenna E
JE
Achenbach
Mucosal and Vaccine Research Colorado (MAVRC), University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Denver Veterans Affairs Medical Center, Denver, CO 80220, USA.
Claire E
CE
Gustafson
Mucosal and Vaccine Research Colorado (MAVRC), University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Kristina A
KA
Stoermer
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Monica
M
Nolan
Makerere University - Johns Hopkins University, Kampala, Uganda.
Laura A
LA
Guay
Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
Thomas K
TK
Leitner
Makerere University - Johns Hopkins University, Kampala, Uganda.
Flavia
F
Matovu
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Allan W
AW
Taylor
Makerere University - Johns Hopkins University, Kampala, Uganda.
Mary Glenn
MG
Fowler
Mucosal and Vaccine Research Colorado (MAVRC), University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Denver Veterans Affairs Medical Center, Denver, CO 80220, USA. Electronic address: Edward.Janoff@ucdenver.edu.
Edward N
EN
Janoff
D000328:Adult; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000032:analysis / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000737:chemistry / Q000276:immunology*; D008895:Milk, Human / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016415:Sequence Alignment; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G
Breast milk; HIV; IgG, IgA; Mucosal immunity; Neutralization; Subtype A; Subtype D; Uganda