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M9630589.TXT
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1996-02-27
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Document 0589
DOCN M9630589
TI Studies of complement-activating antibodies in the SIV/macaque model of
acute primary infection and vaccine protection.
DT 9603
AU Montefiori DC; Reimann KA; Letvin NL; Zhou J; Hu SL; Department of
Surgery, Duke University Medical Center, Durham,; North Carolina 27710,
USA.
SO AIDS Res Hum Retroviruses. 1995 Aug;11(8):963-70. Unique Identifier :
AIDSLINE MED/96020097
AB Questions regarding the potential impact of complement-activating
antibodies on lentivirus pathogenesis and vaccine development were
addressed in the SIV/macaque model by evaluating sera for activity
related to complement-mediated, antibody-dependent enhancement (C'-ADE)
of SIV infection in vitro. C'-ADE activity in sera obtained during acute
primary infection in macaques inoculated with SIVmac251 appeared before
neutralizing antibodies and coincided with the initial peak and decline
of plasma antigenemia. The power of C'-ADE activity (i.e., virus
production measured by p24 immunoassay) decreased as titers of
neutralizing antibodies increased in these animals, suggesting a balance
in the net effect between C'-ADE and neutralizing activities in vitro.
Antibodies with C'-ADE activity were also induced in macaques immunized
with live-attenuated SIVmac239/nef-deletion or primed with recombinant
SIVmne gp120 vaccinia virus and boosted with SIVmne rgp160. The titer
(i.e., last serum dilution to show enhancement), peak (i.e., serum
dilution producing the greatest enhancement as measured by p24
production), and power (i.e., magnitude of p24 production at the peak
titer) of C'-ADE activity in sera obtained from vaccinated macaques on
the day of challenge were comparable to those of sera from infected
macaques and showed no correlation with vaccine outcome, where some
protected animals had C'-ADE profiles that resembled those of
unprotected animals. The results of these studies suggest that
antibodies having C'-ADE activity in vitro could contribute to virus
replication or, alternatively, to virus clearance during the acute stage
of SIV infection in macaques.(ABSTRACT TRUNCATED AT 250 WORDS)
DE Animal Antibodies, Viral/*IMMUNOLOGY Complement Activation/*IMMUNOLOGY
Macaca Recombinant Proteins/GENETICS/IMMUNOLOGY Simian Acquired
Immunodeficiency Syndrome/*IMMUNOLOGY/PREVENTION & CONTROL Support,
U.S. Gov't, P.H.S. SIV/*IMMUNOLOGY Vaccination Viral Envelope
Proteins/GENETICS/IMMUNOLOGY Viral Vaccines/ADMINISTRATION &
DOSAGE/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).