Adenovirus, Serological Surveys Of New Influenza Vaccine Research And Population-based Adenovirus Vector Of Enterovirus

Influenza viruses are the main causative agents for influenza infection.Hemagglutinin (HA) is the most immunogenic antigen on the surface of influenza virus,which can stimulate robust neutralizing antibodies in the host. Novel universal influenzavaccines based on HA by using various strategies became a hotspot in the preventionand control of influenza infection.Adenoviral vector has many advantages as a vaccine vector, such as high-level ofexpression, being able to induce both humoral and cellular immunity, good safety, etc.Until now, most adenoviral vectors are based on human serotype5(AdHu5). This virusis highly epdemic in humans, and AdHu5-specific neutralizing antibodies were found inup to40–60%of human poupulation. Pre-existing neutralizing antibodies dampen genetransfer efficacy and increase vector-mediated toxicity. Thus the use of AdHu5in clinicresearch is limited largely. Novel adenoviral vectors based on rare human serotypes orfrom other species are being explored to overcome the impact of pre-existing immunity.Chimpanzee-origin adenoviruses have been considered as a good choice as vaccinevectors for their low seroprevalence in humans.In this study, various types of influenza virus HA were cloned to chimpanzeeadenovirus type68(AdC68) vector, respectively, to generate the recombinantadenovirus expressing HAs as universal influenza vaccines. In total, nine subtype ofHAs from H1N1, H2N2, H3N2, H4N2, H5N1, H6N6, H7N2, H9N2, and H7N9wereobtained by reverse transcription polymerase chain reaction (RT-PCR), and then clonedto AdC68vector, respectively. The corresponding recombinant adenoviruses wererescued and expanded. AdC68expressing H7N9HA was particularly studied for itsimmune responses induced in animals. Results showed that H7N9-HA specifichemagglutin inhibition antibodies could be elicited by vaccination with AdC68H7N9HA alone or by priming with pShuttle H7N9HA and then boosting with AdC68H7N9HA. Subtype IgG measured by ELISA revealed that IgG2b was higher than IgG1in above vaccination groups. IgG2b is correlated with Th1type of cellular immunity.Therefore, AdC68-H7N9HA effectively activated both humoral and cellular immuneresponses in mice, which implys that adenovirus expressing HA could be a goodvaccine candidate against influenza infection. Hand, foot, and mouth disease (HFMD) is an important public health problem thathas emerged over the past few years. HFMD predominantly infects children under7years old, and occasionally occurs in adults with serious syndrome. Among theenterovirus, Enterovirus71(EV71) and Coxsackievirus16(CA16) are the majorpathogens of HFMD, while adenovirus co-circulates with enterovirus and becameanother possible pathogenetic factor for HFMD in some cases. Here we investigated theneutralizing antibody responses to both enterovirus and adenovirus in adults aiming toexplore the prevalence trends of these viruses, and the nature of protective immunity inhumans to these viral infections. Three hundred ninety one healthy adults fromtwenty-one provinces and cities in China were tested for serum antibodies against EV71,CA16, adenovirus human serotype5(AdHu5), and chimpanzee adenovirus pan7(AdC7)with neutralization tests. High seroprevalence rates of EV71, CA16, and AdHu5werefound in the population (85.7%,58.8%, and74.2%, respectively). The co-seropositivityrate of these three viruses was39.4%(154of391) with median neutralizing antibodytiters of80,40, and640, respectively, and the neutralization titer of EV71correlateswith those of CA16, and AdHu5. AdC7was found to be a rare serotype adenovirus inhuman population, with a seropositivity rate of11.8%, suggesting that it might be agood choice as a vaccine carrier for vaccine development due to its low rate ofneutralizing antibodies in humans.