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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.<\/jats:p>","DOI":"10.1128\/jvi.01102-10","type":"journal-article","created":{"date-parts":[[2010,9,16]],"date-time":"2010-09-16T01:49:26Z","timestamp":1284601766000},"page":"12429-12436","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy"],"prefix":"10.1128","volume":"84","author":[{"given":"Jose\u0301 Maria","family":"Marcelino","sequence":"first","affiliation":[{"name":"Unidade de Tecnologias de Protei\u0301nas e Anticorpos Monoclonais, Instituto de Higiene e Medicina Tropical, Estrada Pac\u0327o Lumiar 22, 1649-038 Lisbon, Portugal"}]},{"given":"Pedro","family":"Borrego","sequence":"additional","affiliation":[{"name":"Centro de Investigac\u0327a\u0303o Interdisciplinar Egas Moniz, Instituto Superior de Cie\u0302ncias da Sau\u0301de Egas Moniz, Quinta Granja, Campus Universita\u0301rio, Monte de Caparica, 2829-511 Caparica, Portugal"},{"name":"Unidade dos Retrovi\u0301rus e Infecc\u0327o\u0303es Associadas, Centro de Patoge\u0301nese Molecular, Faculdade de Farma\u0301cia de Lisboa, Avenida das Forc\u0327as Armadas, 1649-019 Lisbon, Portugal"}]},{"given":"Cheila","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro de Investigac\u0327a\u0303o Interdisciplinar Egas Moniz, Instituto Superior de Cie\u0302ncias da Sau\u0301de Egas Moniz, Quinta Granja, Campus Universita\u0301rio, Monte de Caparica, 2829-511 Caparica, Portugal"},{"name":"Unidade dos Retrovi\u0301rus e Infecc\u0327o\u0303es Associadas, Centro de Patoge\u0301nese Molecular, Faculdade de Farma\u0301cia de Lisboa, Avenida das Forc\u0327as Armadas, 1649-019 Lisbon, Portugal"}]},{"given":"Helena","family":"Barroso","sequence":"additional","affiliation":[{"name":"Centro de Investigac\u0327a\u0303o Interdisciplinar Egas Moniz, Instituto Superior de Cie\u0302ncias da Sau\u0301de Egas Moniz, Quinta Granja, Campus Universita\u0301rio, Monte de Caparica, 2829-511 Caparica, Portugal"},{"name":"Unidade dos Retrovi\u0301rus e Infecc\u0327o\u0303es Associadas, Centro de Patoge\u0301nese Molecular, Faculdade de Farma\u0301cia de Lisboa, Avenida das Forc\u0327as Armadas, 1649-019 Lisbon, Portugal"}]},{"given":"Alexandre","family":"Quintas","sequence":"additional","affiliation":[{"name":"Centro de Investigac\u0327a\u0303o Interdisciplinar Egas Moniz, Instituto Superior de Cie\u0302ncias da Sau\u0301de Egas Moniz, Quinta Granja, Campus Universita\u0301rio, Monte de Caparica, 2829-511 Caparica, Portugal"}]},{"given":"Carlos","family":"Novo","sequence":"additional","affiliation":[{"name":"Unidade de Tecnologias de Protei\u0301nas e Anticorpos Monoclonais, Instituto de Higiene e Medicina Tropical, Estrada Pac\u0327o Lumiar 22, 1649-038 Lisbon, Portugal"}]},{"given":"Nuno","family":"Taveira","sequence":"additional","affiliation":[{"name":"Centro de Investigac\u0327a\u0303o Interdisciplinar Egas Moniz, Instituto Superior de Cie\u0302ncias da Sau\u0301de Egas Moniz, Quinta Granja, Campus Universita\u0301rio, Monte de Caparica, 2829-511 Caparica, Portugal"},{"name":"Unidade dos Retrovi\u0301rus e Infecc\u0327o\u0303es Associadas, Centro de Patoge\u0301nese Molecular, Faculdade de Farma\u0301cia de Lisboa, Avenida das Forc\u0327as Armadas, 1649-019 Lisbon, Portugal"},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisbon, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.5.977"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti770"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(94)90114-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07352"},{"key":"e_1_3_2_6_2","first-page":"319","volume":"16","unstructured":"Barouch, D. 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