Risk Assessment of H2N2 Influenza Viruses from the Avian Reservoir

Abstract

H2N2 influenza A viruses were the cause of the 1957-1958 pandemic. Historical evidence demonstrates they arose from avian virus ancestors, and while the H2N2 subtype has disappeared from humans, it persists in wild and domestic birds. Reemergence of H2N2 in humans is a significant threat due to the absence of humoral immunity in individuals under the age of 50. Thus, examination of these viruses, particularly those from the avian reservoir, must be addressed through surveillance, characterization, and antiviral testing. The data presented here are a risk assessment of 22 avian H2N2 viruses isolated from wild and domestic birds over 6 decades. Our data show that they have a low rate of genetic and antigenic evolution and remained similar to isolates circulating near the time of the pandemic. Most isolates replicated in mice and human bronchial epithelial cells, but replication in swine tissues was low or absent. Multiple isolates replicated in ferrets, and 3 viruses were transmitted to direct-contact cage mates. Markers of mammalian adaptation in hemagglutinin (HA) and PB2 proteins were absent from all isolates, and they retained a preference for avian-like ␣2,3-linked sialic acid receptors. Most isolates remained antigenically similar to pandemic A/Singapore/1/57 (H2N2) virus, suggesting they could be controlled by the pandemic vaccine candidate. All viruses were susceptible to neuraminidase inhibitors and adamantanes. Nonetheless, the sustained pathogenicity of avian H2N2 viruses in multiple mammalian models elevates their risk potential for human infections and stresses the need for continual surveillance as a component of prepandemic planning.

Migratory birds in southern Brazil are a source of multiple avian influenza virus subtypes

“…After 21 days, blood was collected to test for seroconversion by HI assay with turkey red blood cells 37, 38. The HI assay was conducted in triplicate, and the titers are reported as the geometric means.…”

In Vitro Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza Virus Challenge in Mice

“…This virus caused disease in mice and pigs following intranasal inoculation (7)(8)(9), and characterization of several additional avian H2N2 viruses demonstrated that many isolates could replicate in mice and in human bronchial epithelial cells (9,10). In contact transmission studies, both avian H2 and swine H2N3 viruses transmitted efficiently in ferrets, and sequence analysis indicated that these viruses rapidly acquire mutations in the hemagglutinin (HA) receptor-binding site (7,11).…”

Adaptation of Pandemic H2N2 Influenza A Viruses in Humans

“…Jones et al (35) provided a comprehensive risk assessment for the potential reintroduction in humans of H2N2 viruses currently circulating in wild birds and found that while the risk was low, these viruses exhibited pathogenicity, replicative competency, and direct-contact transmission in experimental mammalian systems. Moreover, a lack of sustained systematic global influenza surveillance in birds and other animals severely limits the power of any risk assessment.…”