title: Cross-reactive neutralizing humoral immunity does not protect from HIV type 1 disease progression.
abstract: Broadly reactive neutralizing antibodies are the focus of human immunodeficiency virus (HIV) type 1 vaccine design. However, only little is known about their role in acquired immunodeficiency syndrome (AIDS) pathogenesis and the factors associated with their development. Here we used a multisubtype panel of 23 HIV-1 variants to determine the prevalence of cross-reactive neutralizing activity in serum samples obtained approximately 35 months after seroconversion from 82 HIV-1 subtype B-infected participants from the Amsterdam Cohort Studies on HIV Infection and AIDS. Of these patients, 33%, 48%, and 20%, respectively, had strong, moderate, or absent cross-reactive neutralizing activity in serum. Viral RNA load at set point and AIDS-free survival were similar for the 3 patient groups. However, higher cross-reactive neutralizing activity was significantly associated with lower CD4(+) T cell counts before and soon after infection. Our findings underscore the importance of vaccine-elicited immunity in protecting from infection. The association between CD4(+) T cell counts and neutralizing humoral immunity may provide new clues as to how to achieve this goal.
authors.affiliation: Department of Experimental Immunology, Landsteiner Laboratory Sanquin Research, and Center for Infection and Immunity, Academic Medical Center at the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Zelda
authors.initials: Z
authors.lastname: Euler
authors.forename: Marit J
authors.initials: MJ
authors.lastname: van Gils
authors.forename: Evelien M
authors.initials: EM
authors.lastname: Bunnik
authors.forename: Pham
authors.initials: P
authors.lastname: Phung
authors.forename: Becky
authors.initials: B
authors.lastname: Schweighardt
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003429:Cross Reactions; D018450:Disease Progression; D018572:Disease-Free Survival; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D018451:Homosexuality, Male; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009500:Neutralization Tests / Q000379:methods; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D018709:Statistics, Nonparametric; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012367:RNA, Viral