HIV-1 vaccine induced immune responses in newborns of HIV-1 infected mothers

被引:46
作者
McFarland, Elizabeth J.
Johnson, Daniel C.
Muresan, Petronella
Fenton, Terence
Tomaras, Georgia D.
McNamara, James
Read, Jennifer S.
Douglas, Steven D.
Deville, Jaime
Gurwith, Marc
Gurunathan, Sanjay
Lambert, John S.
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Pediat Infect Dis, Denver, CO USA
[2] Sinai Childrens Hosp, Chicago, IL USA
[3] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA
[4] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA
[6] NIAID, Clin Immunol Branch, Div Allergy & Immunol Transplantat, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[7] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[8] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[9] Univ Calif Los Angeles, Div Pediat Infect Dis, Los Angeles, CA USA
[10] VaxGen Inc, Brisbane, CA USA
[11] Sanofi Pasteur Inc, Swiftwater, PA USA
[12] Mater Misericordiae Univ Hosp, Dublin, Ireland
[13] Univ Coll Dublin, Dublin 2, Ireland
关键词
AIDS vaccine; anti-viral antibodies; cellular immunity; newborn infant; viral vaccines; HIV-1; vertical transmission; mother-to-child-transmission of HIV-1;
D O I
10.1097/01.aids.0000237363.33994.45
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: Breast milk transmission continues to account for a large proportion of cases of mother-to-child transmission of HIV-1 worldwide. An effective HIV-1 vaccine coupled with either passive immunization or short-term antiretroviral prophylaxis represents a potential strategy to prevent breast milk transmission. This study evaluated the safety and immunogenicity of ALVAC HIV-1 vaccine with and without a subunit envelope boost in infants born to HIV-1-infected women. Design: Placebo-controlled, double-blinded study. Methods: Infants born to HIV-1-infected mothers in the US were immunized with a prime-boost regimen using a canarypox virus HIV-1 vaccine (vCP1452) and a recombinant glycoprotein subunit vaccine (rgp120). Infants (n = 30) were randomized to receive: vCP1452 alone, vCP1452 + rgp120, or corresponding placebos. Results: Local reactions were mild or moderate and no significant systemic toxicities occurred. Subjects receiving both vaccines had gp120-specific binding serum antibodies that were distinguishable from maternal antibody. Repeated gp160-specific lymphoproliferative responses were observed in 75%. Neutralizing activity to HIV-1 homologous to the vaccine strain was observed in 50% of the vCP1452 + rgp-120 subjects who had lost maternal antibody by week 24. In some infants HIV-1-specific proliferative and antibody responses persisted until week 104. HIV-1-specific cytotoxic T lymphocyte responses were detected in two subjects in each treatment group; the frequency of HIV-1 specific cytotoxic T lymphocyte responses did not differ between vaccine and placebo recipients. Conclusion: The demonstration of vaccine-induced immune responses in early infancy supports further study of HIV-1 vaccination as a strategy to reduce breast milk transmission. (c) 2006 Lippincott Williams & Wilkins.
引用
收藏
页码:1481 / 1489
页数:9
相关论文
共 38 条
[1]   Neonatal adaptive immunity comes of age [J].
Adkins, B ;
Leclerc, C ;
Marshall-Clarke, S .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :553-564
[2]   Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus type 1 vaccine with or without gp120: A phase 2 study in higher- and lower-risk volunteers [J].
Belshe, RB ;
Stevens, C ;
Gorse, GJ ;
Buchbinder, S ;
Weinhold, K ;
Sheppard, H ;
Stablein, D ;
Self, S ;
McNamara, J ;
Frey, S ;
Flores, J ;
Excler, JL ;
Klein, M ;
El Habib, R ;
Duliege, AM ;
Harro, C ;
Corey, L ;
Keefer, M ;
Mulligan, M ;
Wright, P ;
Celum, C ;
Judson, F ;
Mayer, K ;
McKirnan, D ;
Marmor, M ;
Woody, G .
JOURNAL OF INFECTIOUS DISEASES, 2001, 183 (09) :1343-1352
[3]   Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers [J].
Belshe, RB ;
Gorse, GJ ;
Mulligan, MJ ;
Evans, TG ;
Keefer, MC ;
Excler, JL ;
Duliege, AM ;
Tartaglia, J ;
Cox, WI ;
McNamara, J ;
Hwang, KL ;
Bradney, A ;
Montefiori, D ;
Weinhold, KJ .
AIDS, 1998, 12 (18) :2407-2415
[4]   Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection [J].
Betts, MR ;
Exley, B ;
Price, DA ;
Bansal, A ;
Camacho, ZT ;
Teaberry, V ;
West, SM ;
Ambrozak, DR ;
Tomaras, G ;
Roederer, M ;
Kilby, JM ;
Tartaglia, J ;
Belshe, R ;
Gao, F ;
Douek, DC ;
Weinhold, KJ ;
Koup, RA ;
Goepfert, P ;
Ferrari, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (12) :4512-4517
[5]   Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines [J].
Borkowsky, W ;
Wara, D ;
Fenton, T ;
McNamara, J ;
Kang, MH ;
Mofenson, L ;
McFarland, E ;
Cunningham, C ;
Duliege, AM ;
Francis, D ;
Bryson, Y ;
Burchett, S ;
Spector, SA ;
Frenkel, LM ;
Starr, S ;
Van Dyke, R ;
Jimenez, E .
JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (03) :890-896
[6]   Prevention of mother-to-child transmission of HIV-1 through breast-feeding: Past, present, and future [J].
Bulterys, M ;
Fowler, MG ;
Van Rompay, KK ;
Kourtis, AP .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (12) :2149-2153
[7]   Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1 [J].
Bures, R ;
Gaitan, A ;
Zhu, TF ;
Graziosi, C ;
McGrath, KM ;
Tartaglia, J ;
Caudrelier, P ;
EL Habib, R ;
Klein, M ;
Lazzarin, A ;
Stablein, DM ;
Deers, M ;
Corey, L ;
Greenberg, ML ;
Schwartz, DH ;
Montefiori, DC .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2000, 16 (18) :2019-2035
[8]   T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV [J].
Clerici, M ;
Saresella, M ;
Colombo, F ;
Fossati, S ;
Sala, N ;
Bricalli, D ;
Villa, ML ;
Ferrante, P ;
Dally, L ;
Vigano, A .
BLOOD, 2000, 96 (12) :3866-3871
[9]   Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response [J].
Connick, E ;
Lederman, MM ;
Kotzin, BL ;
Spritzler, J ;
Kuritzkes, DR ;
St Clair, M ;
Sevin, AD ;
Fox, L ;
Chiozzi, MH ;
Leonard, JM ;
Rousseau, F ;
Roe, JD ;
Martinez, A ;
Kessler, H ;
Landay, A .
JOURNAL OF INFECTIOUS DISEASES, 2000, 181 (01) :358-363
[10]  
Coutsoudis A, 2004, J INFECT DIS, V189, P2154, DOI 10.1086/420834