Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine)

Abstract

Please cite this paper as: Gambaryan et al. (2011) Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models. Parallel testing of killed and live H5 vaccine. Influenza and Other Respiratory Viruses 6(3), 188–195. Objective Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Method Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non‐glycoprotein genes of the experimental live vaccines were from H2N2 cold‐adapted master strain A/Leningrad/134/17/57 (VN‐Len and Ku‐Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN‐Gull and Ku‐Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. Results All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold‐adapted H1N1 vaccine reduced the mortality near to zero level. Conclusions The high yield, safety, and protectivity of VN‐Len and Ku‐Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses.

Immunization with live nonpathogenic H5N3 duck influenza virus protects chickens against highly pathogenic H5N1 virus

“…Viruses A/Gull/ Moscow/3100/2006 (gull/3100) and A/duck/Moscow/4182/2008 (dk/4182) were isolated from avian feces collected on the shore of a pond in Moscow, Russia (Lomakina et al, 2009;Boravleva et al, 2012). Attenuation of the highly pathogenic H5N1 virus isolate A/ Chicken/Kurgan/3/05 was described previously Gambaryan et al, 2012). The cold-adapted reassortants rVnLen and rKu-Len and reassortants with HA from either rVN-PR8 or Ku-at and 7 other gene segments from the avian H6N2 virus A/gull/Moscow/3100/2006 were produced as described elsewhere Gambaryan et al, 2012).…”

“…Attenuation of the highly pathogenic H5N1 virus isolate A/ Chicken/Kurgan/3/05 was described previously Gambaryan et al, 2012). The cold-adapted reassortants rVnLen and rKu-Len and reassortants with HA from either rVN-PR8 or Ku-at and 7 other gene segments from the avian H6N2 virus A/gull/Moscow/3100/2006 were produced as described elsewhere Gambaryan et al, 2012). Virus stocks were propagated in the allantoic cavity of 10-day-old embryonated SPF chicken eggs.…”

“…Previously we reported that wild-type А/duck/Moscow/ 4182/2010 virus and reassortants rVN-gull, rKu-gull rVN- Len, and rKu-Len generated in our laboratory were safe for mice and provided protection against HPAI H5N1 virus Gambaryan et al, 2012). Here we compared the pathogenicity of these viruses for chickens (Table 2).…”

“…These experimental live H5 vaccines were nonpathogenic for mice and provided protection against challenge with HPAIV infection 4 weeks after immunization. Preliminary testing demonstrated that these strains can protect chickens against highly pathogenic H5N1 virus Gambaryan et al, 2012).…”

Live poultry vaccines against highly pathogenic avian influenza viruses

“…These viruses inherited the same HA genes as two viruses described above -from VN and Ku/att viruses respectively, while all the other genes were originated from A/ gull/Moscow/3100/2006 virus. The obtained reassortants were named as VN-Gull and Ku-Gull respectively [51][52][53][54].…”