Passive immunization against oral AIDS virus transmission: an approach to prevent mother-to-infant HIV-1 transmission?
To develop immunoprophylaxis regimens against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, we established a simian-human immunodeficiency virus (SHIV) model in neonatal macaques that mimics intrapartum mucosal virus exposure (T.W. Baba, J. Koch, E.S. Mittler et al: AIDS Res Hum Retroviruses 10:351-357, 1994). We protected four neonates from oral SHIV-vpu+ challenge by ante- and postpartum treatment with a synergistic triple combination of immunoglobulin (Ig) G1 human anti-HIV-1 neutralizing monoclonal antibodies (mAbs) (T.W. Baba, V. Liska, R. Hofmann-Lehmann et al: Nature Med 6:200-206, 2000), which recognize the CD4-binding site of Env, a glycosylation-dependent gp120, or a linear gp41 epitope. Two neonates that received only postpartum mAbs were also protected from oral SHIV-vpu+ challenge, indicating that postpartum treatment alone is sufficient. Next, we evaluated a similar mAb combination against SHIV89.6P, which encodes env of primary HIV89.6. One of four mAb-treated neonates was protected from infection and two maintained normal CD4+ T-cell counts. We conclude that the epitopes recognized by the three mAbs are important determinants for achieving protection. Combination immunoprophylaxis with synergistic mAbs seems promising to prevent maternal HIV-1 transmission in humans.
Hofmann-Lehmann
R
R
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115-6084, USA.
Rasmussen
R A
RA
Vlasak
J
J
Smith
B A
BA
Baba
T W
TW
Liska
V
V
Montefiori
D C
DC
McClure
H M
HM
Anderson
D C
DC
Bernacky
B J
BJ
Rizvi
T A
TA
Schmidt
R
R
Hill
L R
LR
Keeling
M E
ME
Katinger
H
H
Stiegler
G
G
Posner
M R
MR
Cavacini
L A
LA
Chou
T C
TC
Ruprecht
R M
RM
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000635:transmission*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002678:Chimera; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000627:therapeutic use; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008253:Macaca mulatta; D008297:Male; D049590:Postpartum Period; D011247:Pregnancy; D015302:Simian Immunodeficiency Virus / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G