title: Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa.
abstract: Clade C is one of the most prevalent genetic subtypes of human immunodeficiency virus type 1 (HIV-1) in the world today and one of the least studied with respect to neutralizing antibodies. Most information on HIV-1 serology as it relates to neutralization is derived from clade B. Clade C primary isolates of HIV-1 from South Africa and Malawi were shown here to resemble clade B isolates in their resistance to inhibition by soluble CD4 and their sensitivity to neutralization by human monoclonal antibody immunoglobulin G1b12 and, to a lesser extent, 2F5. Unlike clade B isolates, however, all 16 clade C isolates examined resisted neutralization by 2G12. Infection with clade C HIV-1 in a cohort of female sex workers in South Africa generated antibodies that neutralized the autologous clade C isolate and T-cell-line-adapted (TCLA) strains of clade B. Neutralization of clade B TCLA strains was much more sensitive to the presence of autologous gp120 V3 loop peptides compared to the neutralization of clade C isolates in most cases. Thus, the native structure of gp120 on primary isolates of clade C will likely pose a challenge for neutralizing antibody induction by candidate HIV-1 vaccines much the same as it has for clade B. The autologous neutralizing antibody response following primary infection with clade C HIV-1 in South Africa matured slowly, requiring at least 4 to 5 months to become detectable. Once detectable, extensive cross-neutralization of heterologous clade C isolates from South Africa was observed, suggesting an unusual degree of shared neutralization determinants at a regional level. This high frequency of cross-neutralization differed significantly from the ability of South African clade C serum samples to neutralize clade B isolates but did not differ significantly from results of other combinations of clade B and C reagents tested in checkerboard assays. Notably, two clade C serum samples obtained after less than 2 years of infection neutralized a broad spectrum of clade B and C isolates. Other individual serum samples showed a significant clade preference in their neutralizing activity. Our results suggest that clades B and C are each comprised of multiple neutralization serotypes, some of which are more clade specific than others. The clustering of shared neutralization determinants on clade C primary HIV-1 isolates from South Africa suggests that neutralizing antibodies induced by vaccines will have less epitope diversity to overcome at a regional level.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Bures
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Gita
authors.initials: G
authors.lastname: Ramjee
authors.forename: Mark
authors.initials: M
authors.lastname: Deers
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Salim
authors.initials: S
authors.lastname: Abdool-Karim
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA; D011477:Sex Work; D013019:South Africa
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments