International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: Correlates of high Ad5 titers and implications for potential HIV vaccine trials

被引:231
作者
Mast, T. Christopher [1 ]
Kierstead, Lisa [1 ]
Gupta, Swati B. [1 ]
Nikas, Alexander A. [1 ]
Kallas, Esper G. [2 ,3 ]
Novitsky, Vladimir [4 ]
Mbewe, Bernard [5 ]
Pitisuttithum, Punee [6 ]
Schechter, Mauro [7 ]
Vardas, Eftyhia [8 ]
Wolfe, Nathan D. [9 ]
Aste-Amezaga, Miguel [1 ]
Casimiro, Danilo R. [1 ]
Coplan, Paul [1 ]
Straus, Walter L. [1 ]
Shiver, John W. [1 ]
机构
[1] Merck Res Labs, West Point, PA USA
[2] Univ Fed Sao Paulo, Sao Paulo, Brazil
[3] Univ Sao Paulo, Sao Paulo, Brazil
[4] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA
[5] Malawi Coll Med, Blantyre, Malawi
[6] Mahidol Univ, Fac Trop Med, Bangkok 10700, Thailand
[7] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil
[8] Univ Witwatersrand, JHB, Perinatal HIV Res Unit, ZA-2050 Wits, South Africa
[9] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA
关键词
Vector; Adenovirus; HIV; Vaccine; IMMUNODEFICIENCY-VIRUS TYPE-1; REPLICATION-DEFECTIVE ADENOVIRUS; VECTOR-BASED VACCINES; RHESUS-MONKEYS; ANTI-AD5; IMMUNITY; HEALTHY-ADULTS; GENE-TRANSFER; IMMUNOGENICITY; INFECTION; RESPONSES;
D O I
10.1016/j.vaccine.2009.10.145
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Replication-defective adenoviruses have been utilized as candidate HIV vaccine vectors Few studies have described the international epidemiology of pre-existing immunity to adenoviruses We enrolled 1904 participants in a cross-sectional serological survey at seven sites in Africa, Brazil, and Thailand to assess neutralizing antibodies (NA) for adenovirus types Ad5, Ad6, Ad26 and Ad36 Clinical trial samples were used to assess NA titers from the US and Europe The proportions of participants that were negative were 14 8%(Ad5), 31 5%(Ad6),41 2%(Ad26) and 53.6% (Ad36) Adenovirus NA titers varied by geographic location and were higher in non-US and non-European settings, especially Thailand In multivariate logistic regression analysis, geographic setting (non-US and non-European settings) was statistically significantly associated with having higher Ad5 titers, participants from Thailand had the highest odds of having high Ad5 titers (adjusted OR = 3 53,95% CI 224,557) Regardless of location. titers of Ad5NA were the highest and Ad36 NA were the lowest Coincident Ad5/6 titers were lower than either Ad5 or Ad6 titers alone Understanding pre-existing immunity to candidate vaccine vectors may contribute to the evaluation of vaccines in international populations (C) 2009 Published by Elsevier Ltd
引用
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页码:950 / 957
页数:8
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