Abstract
ABSTRACTHuman and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5. However, baseline immunity to these vectors still exists in human populations. Traditional cloning of new adenovirus vaccine vectors is a long and cumbersome process that takes 2 months or more and that requires rare unique restriction enzyme sites. Here we describe a novel, restriction enzyme-independent method for rapid cloning of new adenovirus vaccine vectors that reduces the total cloning procedure to 1 week. We developed 14 novel adenovirus vectors from rhesus monkeys that can be grown to high titers and that are immunogenic in mice. All vectors grouped with the unusual adenovirus species G and show extremely low seroprevalence in humans. Rapid cloning of novel adenovirus vectors is a promising approach for the development of new vector platforms. Rhesus adenovirus vectors may prove useful for clinical development.IMPORTANCE To overcome baseline immunity to human and chimpanzee adenovirus vectors, we developed 14 novel adenovirus vectors from rhesus monkeys. These vectors are immunogenic in mice and show extremely low seroprevalence in humans. Rhesus adenovirus vectors may prove useful for clinical development.
Highlights
Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5
Recombinant adenovirus (Ad) vaccine vectors are being explored for pathogens and diseases such as human immunodeficiency virus (HIV), tuberculosis (TB), Zika virus, malaria, respiratory syncytial virus (RSV), and Ebola as well as for cancer [1,2,3,4,5,6,7]
We previously reported the construction of 3 rhesus adenovirus vectors (RhAd51, RhAd52, and RhAd53) [14]
Summary
Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common adenovirus vectors such as Ad5. IMPORTANCE To overcome baseline immunity to human and chimpanzee adenovirus vectors, we developed 14 novel adenovirus vectors from rhesus monkeys. These vectors are immunogenic in mice and show extremely low seroprevalence in humans. Rare human and chimpanzee adenoviruses are being explored as vaccine vectors [15], but due to their close phylogenetic proximity to common human serotypes, substantial seroprevalence is still detected in human populations, in the developing world [16, 17]. With the advancement of new molecular techniques [24], we describe here a novel and rapid method of constructing adenovirus vectors This method is independent of restriction enzymes, requires far less starting material, and can be applied essentially to any adenovirus serotype
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