Structure of general-population antibody titer distributions to influenza A virus

Abstract

Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population's natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states -naiveté, recent infection, non-recent infection, childhood infection -depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.The distribution of antibodies in a human population is a fossil imprint of the population's past exposure to infectious disease. If individuals' antibody concentrations can be measured accurately, they can be used to infer both the size and timing of past epidemics. The two key post-epidemic processes that need to be measured to make this inference possible are the rate of antibody acquisition and the rate of antibody waning. The rate of antibody acquisition post-infection is rapid (weeks) for most viral pathogens, but more difficult to measure for more complex pathogens that present the immune system with a diverse set of antigens. The rate of antibody waning, however, is rarely measured even for viral pathogens. To correctly translate a population's antibody titer distribution to its epidemic history, accurate measures of both these rates are necessary. To validate that this reconstruction has been done correctly, a large cohort with long-term follow-up and precise antibody measurements would be required. Studies like these are difficult to run and difficult to find in the scientific literature -both in methodological

Rapid and lasting generation of B-cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 disease and convalescence

“…The detection of virus-specific antibodies is regularly employed in the diagnosis of other viral infections including Epstein-Barr virus, Cytomegalovirus, Hepatitis B virus, and Influenza virus (Gulley and Tang, 2008; Krajden et al, 2005; Nhat et al, 2017; Ross et al, 2011). The antibody response to SARS-CoV-2 infection has been shown to be directed to multiple targets of the virus including the spike, with those that target the RBD considered neutralizing (Gudbjartsson et al, 2020; Long et al, 2020; Ng et al, 2020; Vabret et al, 2020).…”

Age-seroprevalence curves for the multi-strain structure of influenza A virus

“…Serum samples used for this analysis come from a serum bank established in 2009 in southern Vietnam and maintained for the purposes of measuring exposure and seroincidence to a range of pathogens 36–42 . Every two months or every four months (depending on the site), 200 residual serum samples are collected from the haematology or biochemistry departments of ten major public hospitals: the Hospital for Tropical Diseases in Ho Chi Minh City, Hue Central Hospital in the city of Hue, Khanh Hoa General Hospital in Nha Trang, Dak Lak Provincial Hospital in Buon Ma Thuot city, Soc Trang General Hospital, Dong Thap General Hospital, Kien Giang General Hospital, Binh Dinh General Hospital, Quang Ngai General Hospital, An Giang General Hospital (Figure 1).…”

“…Approximately 7800 samples are collected each year and the samples are believed to represent the hospital-going population or general population in their respective provinces. For further details on sample collection see Nhat et al 36 . A total of 35,688 serum samples collected between 2009 and 2015 were selected for this analysis.…”

Hepatitis E in southern Vietnam: Seroepidemiology in humans and molecular epidemiology in pigs

“…Selection of Dong Thap province for this substudy was coordinated with a complementary long-term seroepidemiology study from Dong Thap Provincial Hospital (DTPH), with residual samples collected from the hospital haematology laboratory; this was part of an on-going seroepidemiology study being conducted in southern Vietnam (Boni et al, 2013; Nhat et al, 2016). Additionally, Dong Thap province was selected because the high density of domestic livestock and/or farmed wildlife populations, the diversity of local agro-ecosystems, and pre-existing frameworks for collaborative research between Oxford University Clinical Research Unit and Sub-Departments of Preventive Medicine and Animal Health (PMC and SDAH, respectively).…”

“…Each collected specimen contained approximately 0.5 ml of serum. Samples for this seroepidemiology study are stored at −20°C and transported on dry ice twice yearly to Ho Chi Minh City where they are stored at −20°C as part of a central serum bank for southern Vietnam (Boni et al, 2013; Nhat et al, 2016; Thuy et al, 2017).…”