Association between antibody titers and protection against influenza virus infection within households

Abstract

Background: Previous studies have established that antibody titer measured by the hemagglutination-inhibiting (HAI) assay is correlated with protection against influenza virus infection, with an HAI titer of 1:40 generally associated with 50% protection.

Methods: We recruited index cases with confirmed influenza virus infection from outpatient clinics, and followed up their household contacts for 7-10 days to identify secondary infections. Serum samples collected from a subset of household contacts were tested by HAI and microneutralization (MN) assays against prevalent influenza viruses. We analyzed the data using an individual hazard-based transmission model that adjusted for age and vaccination history.

Results: Compared to a reference group with antibody titers <1:10, we found that HAI titers of 1:40 against influenza A(H1N1) and A(H3N2) were associated with 31% (95% confidence interval [CI], 13%-46%) and 31% (CI, 1%-53%) protection against polymerase chain reaction (PCR)-confirmed A(H1N1) and A(H3N2) virus infection, respectively, while an MN titer of 1:40 against A(H3N2) was associated with 49% (95% CI, 7%-81%) protection against PCR-confirmed A(H3N2) virus infection.

Conclusions: An HAI titer of 1:40 was associated with substantially less than 50% protection against PCR-confirmed influenza virus infection within households, perhaps because of exposures of greater duration or intensity in that confined setting.

Keywords: antibody; immunity; influenza; transmission.

Figure 1.

Flow chart of enrollment of index cases with PCR-confirmed influenza virus infection and their household contacts. Abbreviations: PCR, polymerase chain reaction; RT, reverse-transcriptase.

Figure 2.

Timeline of subject recruitment and local influenza virus activity. A, Number of index cases with seasonal influenza A(H1N1) and A(H3N2) recruited over time. B, Proxy measure of seasonal influenza A(H1N1) and A(H3N2) virus activity in Hong Kong based on local surveillance data on influenza-like illness and laboratory detections of influenza.

Figure 3.

Correlation between reciprocal antibody titers and protection against PCR-confirmed influenza virus infection. A, Protection among household contacts of index cases with seasonal influenza A(H1N1) virus infection associated with reciprocal HAI titers against seasonal A(H1N1) virus. B, Protection among household contacts of index cases with seasonal influenza A(H3N2) virus infection associated with reciprocal HAI titers against seasonal A(H3N2) virus. C, Protection among household contacts of index cases with seasonal influenza A(H3N2) virus infection associated with reciprocal MN titers against seasonal A(H3N2) virus. Reciprocal antibody titers corresponding to 50% protection are indicated with gray lines. Abbreviations: HAI, hemagglutination-inhibiting; MN, microneutralization; PCR, polymerase chain reaction.

Figure 4.

Factors affecting household transmission and the household serial interval. A, Estimates of the relative susceptibility of household contacts who were <19 years of age and of those who were >50 years of age (compared to the reference group of contacts who were 19–50 years of age). B, Serial interval distributions estimated under the transmission model, accounting for tertiary and community infections. C, Age-specific estimates of vaccine effectiveness against infection for household contacts. D, Age-specific risk of infection for household contacts, including the risk of secondary and tertiary transmission and infection from outside the household.