Response of Mice and Ferrets to a Monovalent Influenza A (H7N9) Split Vaccine

Abstract

In early spring 2013, the emergence of the influenza A (H7N9) virus in humans in Eastern China raised concerns of a new influenza pandemic. Development of a safe and effective H7N9 influenza vaccine is urgently needed. To this end, we first synthesized the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A (H7N9) virus A/AnHui/1/2013. Using reverse genetics, we rescued a reassortant virus (H7N9/PR8) that contained the HA and NA genes from wild-type H7N9 and six genes encoding internal proteins from the A/Puerto Rico/8/34 (PR8) virus. Next, the pathogenicity of the reassortant virus was evaluated both in vivo and in vitro. We found that the virus was non-pathogenic in mice and was stable after serial passaging in eggs. Furthermore, we found that a monovalent influenza A (H7N9) split vaccine prepared from the virus was immunogenic in mice and ferrets. When given intramuscularly, the vaccine (two doses of at least 15-µg) completely protected mice from normally lethal wild-type H7N9 virus challenge. In summary, our H7N9 vaccine, developed over a short time, is a potential candidate for further clinical evaluation and human use.

Protection from infection with influenza A H7N9 virus in a mouse model by equine neutralizing F(ab′)2

“…Compared with the longer time distance of any vaccines to elicit protective immunity in the healthy hosts, the highly purified F(ab′) 2 fragments against HPAI H7N9 virus could provide immediate protection regardless of the immune status of the host. Meanwhile, there is still a long way to go from bench to bedside for various vaccines against HPAI H7N9 virus under development [7,8].…”

“…The purified inactivated H7N9 virus antigens were prepared according to the same standard techniques that are used for the production of seasonal influenza trivalent inactivated whole virus vaccine [8]. Briefly, Ah01/H7N9 was inoculated in the allantoic cavity of 10-day-old SPF embryonated eggs, harvested 3 days post inoculation and inactivated by formaldehyde in a bio-safety level 3 lab.…”

“…The neutralization titer of the F(ab′) 2 fragments against influenza A H7N9 virus was determined in vitro as previously described [8]. In brief, the F(ab′) 2 fragments were diluted, initially to 2.5 μg/ml as the highest dose, and then by twofold serial dilution in culture medium.…”

“…Several strategies are being used to develop vaccines that protect humans from influenza virus infection, such as inactivated, subunit, and live attenuated vaccines [7][8][9]. Even developed successfully, largescale innoculation of the vaccine may not be one of the best means of controlling the spread of the disease because of the low incidence of new cases of HPAI virus infection [10,11].…”

An update on clinical trials of H7N9 influenza vaccines

“…As for now, the BTBP has got its clinical trial approvals from state FDA and the applications of other three enterprises are now also being accepted [16] . nonhuman primates, their efficacy in human subjects remains to be evaluated [17][18][19] .…”