Synergy in monoclonal antibody neutralization of HIV-1 pseudoviruses and infectious molecular clones

Riccardo Miglietta, Claudia Pastori, Assunta Venuti, Christina Ochsenbauer, Lucia Lopalco

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Early events in HIV infection are still poorly understood; virus derived from acute infections, the transmitted/founders IMCs, could provide more reliable information as they represent strains that established HIV infection in vivo, and therefore are investigated to elucidate potentially shared biological features. Methods: This study examined synergy in neutralization by six monoclonal antibodies targeting different domains in gp120 and gp41 and assayed in pairwise combination against 11 HIV-1 clade B strains, either Env pseudoviruses (PV, n = 5) or transmitted/founder infectious molecular clones (T/F IMCs, n = 6). Three of the early-infection env tested as PV were juxtaposed with T/F viruses derived from the same three patients, respectively. Results: All antibodies reaching IC50 were assayed pairwise (n = 50). T/F IMCs showed overall lower sensitivity to neutralization by single antibodies than PV, including within the three patient-matched pairs. Remarkably, combination index (CI) calculated using the Chow and Talalay method indicated synergy (CI <0.9) in 42 data sets, and occurred in T/F IMC at similar proportions (15 of 17 antibody-T/F IMC combinations tested) as in pseudoviruses (27 of 33). CI values indicative of additivity and low-level antagonism were seen in 5 and 3 cases, respectively. Most pairs showed comparable synergic neutralizing effects on both virus groups, with the 4E10 + PG16 pair achieving the best synergic effects. Variability in neutralization was mostly observed on pseudovirus isolates, suggesting that factors other than virus isolation technology, such as env conformation, epitope accessibility and antibody concentration, are likely to affect polyclonal neutralization. Conclusions: The findings from this study suggest that inhibitory activity of bNAbs can be further augmented through appropriate combination, even against viruses representing circulating strains, which are likely to exhibit a less sensitive Tier 2 neutralization phenotype. This notion has important implications for the design and development of anti-Env bNAb-inducing vaccines and polyclonal sera for passive immunization.

Original languageEnglish
Article number346
JournalJournal of Translational Medicine
Volume12
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Viruses
HIV-1
Clone Cells
Monoclonal Antibodies
Antibodies
HIV Infections
Immunization
Passive Immunization
Infection
Inhibitory Concentration 50
Conformations
Epitopes
Vaccines
Technology
Phenotype
Serum

Keywords

  • HIV neutralization
  • Monoclonal antibody
  • Pseudovirus
  • T/F-IMC

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Synergy in monoclonal antibody neutralization of HIV-1 pseudoviruses and infectious molecular clones. / Miglietta, Riccardo; Pastori, Claudia; Venuti, Assunta; Ochsenbauer, Christina; Lopalco, Lucia.

In: Journal of Translational Medicine, Vol. 12, No. 1, 346, 2014.

Research output: Contribution to journalArticle

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