An H9N2 Influenza Virus Vaccine Prepared from a Non-Pathogenic Isolate from a Migratory Duck Confers Protective Immunity in Mice against Challenge with an H9N2 Virus Isolated from a Girl in Hong Kong

Abstract

ABSTRACT. H9N2 influenza viruses circulate in wild birds and poultry in Eurasian countries, and have been isolated from pigs and humans in China. H9N2 viruses isolated from birds, pigs and humans have been classified into three sublineages based on antigenic and genetic features. Chicken antisera to H9N2 viruses of the Korean sublineage reacted with viruses of different sublineages by the hemagglutination-inhibition test. A test vaccine prepared from a non-pathogenic A/duck/Hokkaido/49/1998 (H9N2) strain of the Korean sublineage, obtained from our influenza virus library, induced immunity in mice to reduce the impact of disease caused by the challenge with A/Hong Kong/1073/1999 (H9N2), which is of a different sublineage. The present results indicate that an inactivated whole virus vaccine prepared from a non-pathogenic influenza virus from the library could be used as an emergency vaccine during the early stage of a pandemic caused by H9N2 infection.

Different outcomes of infection of chickens and ducks with a duck-origin H9N2 influenza A virus

“…Evidence also suggested that lack of secondary immune responses appeared to be a general feature of duck antibody responses (Kida et al, 1980;Lundqvist et al, 2006). Several inactivated influenza vaccines are currently used for controlling avian influenza in the laboratory and field studies (Tian et al, 2005;Nomura et al, 2012;). In one of these studies, vaccination of ducks with inactivated influenza vaccine induced lower antibody titers and required larger dosage in comparison with vaccination of chickens.…”

Vaccination against H9N2 avian influenza virus reduces bronchus‐associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection

“…Cynomolgus macaques were immunized subcutaneously twice with whole virus particles inactivated by formalin prepared from Hok49 without addition of an adjuvant. We used 1 mg of the whole particle vaccine in the macaque model since 10 to 50 μg of the vaccines were required to induce antibody responses in previous mouse studies . Antigen‐specific IgG was detected in sera of macaques two weeks after the first vaccination (Fig.…”

“…The percent amino acid similarities between Hok49 and HK1073 were 89 % and 88 % in HA and NA, respectively. A formalin‐inactivated vaccine was made according to a previous report . The vaccine used in the present study contained 200 000 HA units of HA antigen in one mg vaccine.…”

“…Therefore, additional models mimicking natural infection are required for evaluation of the pathogenicity of H9N2 virus. Several trials of inactivated and live attenuated vaccines against H9N2 virus in mice and humans have been reported . We previously reported that whole particle vaccines prepared from a virus library that contained 144 combinations of 16 HAs and 9 neuraminidases (NAs) conferred protective immune responses against H5N1 and H7N7 highly pathogenic influenza viruses in cynomolgus macaques .…”

“…Second, we examined the immunogenicity and protective effects of a vaccine against challenge with H9N2 virus isolated from a human patient. We selected an H9N2 vaccine strain from the virus library to make a whole virus particle vaccine inactivated by formalin . As a result, we revealed that the H9N2 virus propagated in the upper airways of macaques and induced bronchus‐associated lymphoid tissue (BALT) formation in the lungs and that a whole particle vaccine derived from an avian virus strain induced protective antibody responses and prevented the onset of symptoms in cynomolgus macaques.…”