International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations

Abstract

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4,381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4×1010 vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.

Progress in HIV vaccine development

“…119 Therefore, concern regarding preexisting vector immunity prompted the development of other Ad vectors with lower seroprevalence, including Ad26 and Ad35. 120,121 Ad26 and Ad35 studies have shown potential in phase I/II human vaccine trials. [122][123][124][125] A recent randomized, double-blind, placebo-controlled trial in 218 healthy adults using Ad26.…”

Comparative Analysis of Simian Immunodeficiency Virus Gag-Specific Effector and Memory CD8 + T Cells Induced by Different Adenovirus Vectors

“…Some of the most commonly employed adenovirus vectors are based on the human serotypes 2 and 5 (Ad2 and Ad5), which are highly prevalent (1)(2)(3). Of the 51 known human adenovirus serotypes, Ad5 has been the most widely used vector, but the failed Merck human immunodeficiency virus type 1 (HIV-1) vaccine clinical trial generated skepticism about using adenoviruses as vaccine platforms (4).…”

Adenovirus Serotype 5-Specific Neutralizing Antibodies Target Multiple Hexon Hypervariable Regions

“…We previously reported that replacing all seven hexon HVRs in Ad5 with those from a rare human adenovirus serotype, Ad48, resulted in a chimeric vector, Ad5HVR48 (1)(2)(3)(4)(5)(6)(7), that evaded the majority of preexisting Ad5 immunity in preclinical studies in mice and rhesus monkeys (13). However, the relative importances of the seven individual HVRs as NAb epitopes remain incompletely understood, and recent studies have suggested that Ad5 NAb responses may actually be focused primarily on one specific HVR, such as HVR1 or HVR5 (1,15).…”