title: 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.
abstract: 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: 2.24, 5.57). 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.
authors.affiliation: Merck Research Laboratories, West Point, PA, USA. christopher mast@merck.com
authors.forename: T Christopher
authors.initials: TC
authors.lastname: Mast
authors.forename: Lisa
authors.initials: L
authors.lastname: Kierstead
authors.forename: Swati B
authors.initials: SB
authors.lastname: Gupta
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Nikas
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.forename: Vladimir
authors.initials: V
authors.lastname: Novitsky
authors.forename: Bernard
authors.initials: B
authors.lastname: Mbewe
authors.forename: Punee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Eftyhia
authors.initials: E
authors.lastname: Vardas
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Wolfe
authors.forename: Miguel
authors.initials: M
authors.lastname: Aste-Amezaga
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Paul
authors.initials: P
authors.lastname: Coplan
authors.forename: Walter L
authors.initials: WL
authors.lastname: Straus
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: D000258:Adenovirus Infections, Human / Q000453:epidemiology*; D000260:Adenoviruses, Human / Q000145:classification / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000349:Africa / Q000453:epidemiology; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D001938:Brazil / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D005843:Geography; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D016036:Seroepidemiologic Studies; D013785:Thailand / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral