Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression.
OBJECTIVE
The native envelope gp160 trimer of HIV-1 is thought to shield vulnerable epitopes that could otherwise elicit effectively neutralizing antibodies. However, little is known about the prevalence of naturally occurring broadly neutralizing activity in serum of HIV-1-infected individuals.


METHODS
Here, we studied 35 participants of the Amsterdam Cohort Studies on HIV-1 infection (20 long-term nonprogressors and 15 progressors) for the presence of cross-reactive neutralizing activity in their sera at 2 and 4 years after seroconversion. Neutralizing activity was tested in a pseudovirus assay, against a panel of HIV-1 envelope variants from subtypes A, B, C, and D.


RESULTS
Already at year 2 after seroconversion, seven out of 35 individuals (20%) had cross-reactive neutralizing activity, which increased to 11 individuals (31%) at 4 years after seroconversion. There was no difference in the prevalence of cross-reactive neutralizing serum activity between long-term nonprogressors and progressors.Interestingly, high plasma viral RNA load and low CD4(+) cell count at set-point were associated with early development of cross-reactive neutralizing activity. Neutralization titers in serum increased during the course of infection for 91% of individuals studied here, although less rapidly for those who did not develop cross-reactive neutralizing activity.


CONCLUSIONS
Overall, we here demonstrate a relatively high prevalence of cross-reactive neutralizing serum activity in HIV-1-infected patients, which increased with duration of infection. These data may imply that immunogenicity of the native envelope spike of HIV-1 for eliciting cross-reactive humoral immune responses may be better than previously anticipated.
van Gils
Marit J
MJ
Department of Experimental Immunology, Landsteiner Laboratory Sanquin Research, and Center for Infection and Immunity (CINIMA), Academic Medical Center at the University of Amsterdam, Amsterdam, The Netherlands.
Euler
Zelda
Z
Schweighardt
Becky
B
Wrin
Terri
T
Schuitemaker
Hanneke
H
D057134:Antibodies, Neutralizing / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D003429:Cross Reactions / Q000276:immunology; D018450:Disease Progression; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D012367:RNA, Viral