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.
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.
Mast
T Christopher
TC
Merck Research Laboratories, West Point, PA, USA. christopher mast@merck.com
Kierstead
Lisa
L
Gupta
Swati B
SB
Nikas
Alexander A
AA
Kallas
Esper G
EG
Novitsky
Vladimir
V
Mbewe
Bernard
B
Pitisuttithum
Punee
P
Schechter
Mauro
M
Vardas
Eftyhia
E
Wolfe
Nathan D
ND
Aste-Amezaga
Miguel
M
Casimiro
Danilo R
DR
Coplan
Paul
P
Straus
Walter L
WL
Shiver
John W
JW
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
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral