title: Potent and broadly reactive HIV-2 neutralizing antibodies elicited by a vaccinia virus vector prime-C2V3C3 polypeptide boost immunization strategy.
abstract: Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism.
authors.affiliation: Unidade de Tecnologias de Proteínas e Anticorpos Monoclonais, Instituto de Higiene e Medicina Tropical, Estrada Paço Lumiar 22, Lisbon, Portugal.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Marcelino
authors.forename: Pedro
authors.initials: P
authors.lastname: Borrego
authors.forename: Cheila
authors.initials: C
authors.lastname: Rocha
authors.forename: Helena
authors.initials: H
authors.lastname: Barroso
authors.forename: Alexandre
authors.initials: A
authors.lastname: Quintas
authors.forename: Carlos
authors.initials: C
authors.lastname: Novo
authors.forename: Nuno
authors.initials: N
authors.lastname: Taveira
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015498:HIV-2 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007117:Immunization, Secondary; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology* / Q000378:metabolism; D014616:Vaccinia virus; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D017931:DNA Primers; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C066316:gp125 envelope protein, Human immunodeficiency virus 2