TY - JOUR
T1 - Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression
AU - van Gils, Marit J.
AU - Euler, Zelda
AU - Schweighardt, Becky
AU - Wrin, Terri
AU - Schuitemaker, Hanneke
PY - 2009
Y1 - 2009
N2 - 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, 13, 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. Conclusion: 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. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
AB - 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, 13, 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. Conclusion: 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. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
U2 - https://doi.org/10.1097/QAD.0b013e32833243e7
DO - https://doi.org/10.1097/QAD.0b013e32833243e7
M3 - Article
C2 - 19770692
SN - 0269-9370
VL - 23
SP - 2405
EP - 2414
JO - AIDS (London, England)
JF - AIDS (London, England)
IS - 18
ER -