Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment

Abstract

Background: Influenza A pandemics cause significant mortality and morbidity. H2N2 viruses have caused a prior pandemic, and are circulating in avian reservoirs. The age-related frequency of current population immunity to H2 viruses was evaluated.

Methods: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A(H2N2) viruses were performed across age groups in Rochester, New York, and Hong Kong, China. The impact of existing cross-reactive HAI immunity on the effective reproduction number was modeled.

Results: One hundred fifty individual sera from Rochester and 295 from Hong Kong were included. Eighty-five percent of patients born in Rochester and Hong Kong before 1968 had HAI titers ≥1:40 against A/Singapore/1/57, and >50% had titers ≥1:40 against A/Berkeley/1/68. The frequency of titers ≥1:40 to avian H2N2 A/mallard/England/727/06 and A/mallard/Netherlands/14/07 in subjects born before 1957 was 62% and 24%, respectively. There were no H2 HAI titers >1:40 in individuals born after 1968. These levels of seroprevalence reduce the initial reproduction number of A/Singapore/1/1957 or A/Berkeley/1/68 by 15%-20%. A basic reproduction number (R0) of the emerging transmissible virus <1.2 predicts a preventable pandemic.

Conclusions: Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus. An H2N2 pandemic would have lower impact in those born before 1968.

Figure 1.

Frequency distribution sera with hemagglutination inhibition titers of ≥1:40 to human and avian H2N2 viruses in Hong Kong and Rochester, New York, against A/Singapore/1/57 (S57), A/Berkeley/1/68 (B68), A/mallard/England/727/2006 (M727), and A/mallard/Netherlands/14/07 (M14) among persons born before the circulation of H2N2 viruses (prior to 1957), born during the H2N2 epidemic period (1958–1968), and after H2N2 viruses circulated in humans (after 1968). Abbreviations: H, Hong Kong; HAI, hemagglutination inhibition; R, Rochester, New York.

Figure 2.

Reverse cumulative distribution of antibody titers against human and avian H2 viruses by period of birth. Data from Hong Kong and Rochester, New York, were combined. A hemagglutination inhibition titer of <1: 10 was considered a dilution of 5. Abbreviation: HAI, hemagglutination inhibition.

Figure 3.

Estimations of overall population-level immunity against H2 viruses and the potential impact of population immunity on reproduction number, using 3 potential titer cutoffs for 100% immunity. Bars represent the 95% confidence intervals of the estimates. Data are shown from S57 A/Singapore/1/57, B68 A/Berkeley/1/68, M727 A/mallard/England/727/06, M14 A/mallard/Netherlands/14/07, Hong Kong, and Rochester, New York. Abbreviations: H, Hong Kong; R, Rochester, New York; R₀, basic reproduction number.