Development and Evaluation of an Influenza Virus Subtype H7N2 Vaccine Candidate for Pandemic Preparedness

Abstract

Influenza virus of the H7N2 subtype has been introduced into noncommercial poultry in the United States, and this probably resulted in incidents of transmission of H7N2 virus to humans, documented in 2002 and 2003. This virus could be considered a potential threat to public health if it acquired person-to-person transmissibility. A favored approach for global pandemic preparedness includes development of prepandemic vaccines for any potential pandemic virus. To this end, we created a high-growth reassortant virus (H7N2-PR8) containing the genes for the hemagglutinin and the neuraminidase from a low-pathogenicity (H7N2) virus strain and the remaining six genes from a human vaccine strain (H1N1). The reassortant strain was evaluated to assess its antigenicity, safety, and protective efficacy using a mouse model. Antigenicity studies using ferret antibodies raised against H7N2-PR8 indicated that this virus confers broad cross-reactivity with divergent H7 viruses of different years and lineages. Mice and chickens inoculated with high doses of H7N2-PR8 supported virus replication but survived, indicating that this virus is comparable to other avian viruses of low pathogenicity. To assess the protective efficacy of H7N2-PR8, mice were immunized with two doses of formalininactivated H7N2-PR8, alone or with alum. Vaccinated mice subsequently challenged with highly pathogenic viruses from homologous and heterologous lineages A/Canada/444/04 (H7N3) and A/Netherlands/219/03 (H7N7) showed pronounced reduction of wild-type virus replication. These studies indicate that H7N2-PR8 is immunogenic, safe, and protective in animal models; these are the essential attributes to qualify for phase I human clinical trials as a prepandemic vaccine.

A Live Attenuated H7N7 Candidate Vaccine Virus Induces Neutralizing Antibody That Confers Protection from Challenge in Mice, Ferrets, and Monkeys

“…Formalin-inactivated H7N2/PR8 and H7N7/PR8 whole-virus vaccines with and without aluminum hydroxide adjuvant elicited broadly cross-reactive antibodies against divergent H7 viruses and protected mice against challenge with heterologous H7 wt viruses of both Eurasian and North American lineages (14,19,29). Thus, H7N2, H7N7, H7N1, and H7N3 vaccines have been variably immunogenic yet generally protect experimental animals from challenge with homologous and heterologous H7 viruses.…”

“…Inactivated vaccines against both lineages of H7 viruses on an A/PR/8/34 (PR/8) (H1N1) backbone have been evaluated in preclinical trials (14,19,29). Formalin-inactivated H7N2/PR8 and H7N7/PR8 whole-virus vaccines with and without aluminum hydroxide adjuvant elicited broadly cross-reactive antibodies against divergent H7 viruses and protected mice against challenge with heterologous H7 wt viruses of both Eurasian and North American lineages (14,19,29).…”

“…Vaccines for human use against both lineages of H7 influenza virus are under development, and candidate vaccines have been evaluated in preclinical and clinical studies (14,23,29,42).…”

Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis

“…The frequent reassortment and rapid movement of H7 influenza viruses within this population necessitate continued surveillance of this virus subtype in both wild and domestic birds (54). The continued assessment of H7 viruses detected during routine surveillance, poultry outbreaks, and human infections is critical to both assess the pandemic potential of these strains in humans and characterize laboratory mammalian models suited to examine the efficacy and cross-reactivity of candidate H7 vaccines against viruses within this subtype (34,(55)(56)(57). Because recent H7 subtype viruses associated with poultry outbreaks and surveillance activities possess the ability to cause infection by the ocular route, the use of eye protection to reduce the potential for occupational exposure is prudent (58).…”

Avian Influenza: Public Health and Food Safety Concerns

“…Today, AI viruses of concern as potential pandemic strains are some H5, H7, and H9 subtypes that have crossed the human species barrier multiple times to produce sporadic infections. This will be discussed in following sections (Li et al 2003, WHO 2005, CDC 2007, Webster et al 2007, Pappas et al 2007). …”