IgM, IgG, and IgA Antibody Responses to Influenza A(H1N1)pdm09 Hemagglutinin in Infected Persons during the First Wave of the 2009 Pandemic in the United States

Li, Zhu-Nan; Lin, Seh-Ching; Carney, P.J.; Li, Ji; Liu, Feng; Lu, Xiuhua; Liu, Merry; Stevens, James; Levine, Min Z.; Katz, Jacqueline M.; Hancock, Kathy

doi:10.1128/cvi.00129-14

Cited by 33 publications

(42 citation statements)

References 37 publications

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“…These results suggest that among the antibody profiles to the 19 HAs (from 11 influenza subtypes) measured by MAGPIX, MFI against rHA from the exposed novel HA subtype had the highest correlation to MN titers to the same virus. It is consistent with our previous observation during the first wave of A(H1N1)pdm09 pandemic …”

Section: Resultssupporting

confidence: 94%

Identification of novel influenza A virus exposures by an improved high‐throughput multiplex MAGPIX platform and serum adsorption

Cheng

Poirot

et al. 2019

Influenza Resp Viruses

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Background The development of serologic assays that can rapidly assess human exposure to novel influenza viruses remains a public health need. Previously, we developed an 11‐plex magnetic fluorescence microsphere immunoassay (MAGPIX) by using globular head domain recombinant hemagglutinins (rHAs) with serum adsorption using two ectodomain rHAs. Methods We compared sera collected from two cohorts with novel influenza exposures: animal shelter staff during an A(H7N2) outbreak in New York City in 2016‐2017 (n = 119 single sera) and poultry workers from a live bird market in Bangladesh in 2012‐2014 (n = 29 pairs). Sera were analyzed by microneutralization (MN) assay and a 20‐plex MAGPIX assay with rHAs from 19 influenza strains (11 subtypes) combined with serum adsorption using 8 rHAs from A(H1N1) and A(H3N2) viruses. Antibody responses were analyzed to determine the novel influenza virus exposure. Results Among persons with novel influenza virus exposures, the median fluorescence intensity (MFI) against the novel rHA from exposed influenza virus had the highest correlation with MN titers to the same viruses and could be confirmed by removal of cross‐reactivity from seasonal H1/H3 rHAs following serum adsorption. Interestingly, in persons with exposures to novel influenza viruses, age and MFIs against exposed novel HA were negatively correlated, whereas in persons without exposure to novel influenza viruses, age and MFI against novel HAs were positively correlated. Conclusions This 20‐plex high‐throughput assay with serum adsorption will be a useful tool to detect novel influenza virus infections during influenza outbreak investigations and surveillance, especially when well‐paired serum samples are not available.

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Section: Resultssupporting

confidence: 94%

Identification of novel influenza A virus exposures by an improved high‐throughput multiplex MAGPIX platform and serum adsorption

Cheng

Poirot

et al. 2019

Influenza Resp Viruses

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“…Fold rises in MFI and DPP values (S2 value/S1 value) were calculated to measure antibody binding. Due to wide dynamic ranges of the readout of the MAGPIX and DPP assays, S1 samples with values lower than baseline level were normalized to a set value as discussed previously . For serum samples from US residents, any MFI lower than 1000 in MAGPIX and DPP value lower than 100 in DPP in S1 samples were arbitrarily adjusted to 1000 and 100, respectively.…”

Section: Methodsmentioning

confidence: 99%

Novel multiplex assay platforms to detect influenza A hemagglutinin subtype‐specific antibody responses for high‐throughput and in‐field applications

Trost

Weber

et al. 2017

Influenza Resp Viruses

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BackgroundDetections of influenza A subtype‐specific antibody responses are often complicated by the presence of cross‐reactive antibodies. We developed two novel multiplex platforms for antibody detection. The multiplexed magnetic fluorescence microsphere immunoassay (MAGPIX) is a high‐throughput laboratory‐based assay. Chembio Dual Path Platform (DPP) is a portable and rapid test that could be used in the field.MethodsTwelve recombinant globular head domain hemagglutinin (GH HA1) antigens from A(H1N1)pdm09 (pH1N1), A(H2N2), A(H3N2), A(H5N1), A(H7N9), A(H9N2), A(H13N9), B/Victoria lineage, B/Yamagata lineage viruses, and protein A control were used. Human sera from U.S. residents either vaccinated (with H5N1 or pH1N1) or infected with pH1N1 influenza viruses and sera from live bird market workers in Bangladesh (BDPW) were evaluated. GH HA1 antigens and serum adsorption using full ectodomain recombinant hemagglutinins from A(pH1N1) and A(H3N2) were introduced into the platforms to reduce cross‐reactivity.ResultsSerum adsorption reduced cross‐reactivity to novel subtype HAs. Compared to traditional hemagglutination inhibition or microneutralization assays, when serum adsorption and the highest fold rise in signals were used to determine positivity, the correct subtype‐specific responses were identified in 86%‐100% of U.S. residents exposed to influenza antigens through vaccination or infection (N=49). For detection of H5N1‐specific antibodies in sera collected from BDPW, H5 sensitivity was 100% (six of six) for MAGPIX, 83% (five of six) for DPP, H5 specificity was 100% (15/15), and cross‐reactivity against other subtype was 0% (zero of six) for both platforms.ConclusionMAGPIX and DPP platforms can be utilized for high‐throughput and in‐field detection of novel influenza virus infections.

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“…Since IAV-specific Ab titers were highest during viral clearance, it is unlikely that immediately available Abs in the BAL fluid play a role in IAV neutralization in the allergic hosts. Interestingly, IAV infection results in the increase of both IgE (33) and IgA (34) in humans. Despite observing an increase in IgE + and IgA + cells in the spleen, MLNs, and lungs of Flu-control mice, neither Ab increased over baseline in the BAL fluid or serum.…”

Section: Discussionmentioning

confidence: 99%

Humoral immune responses during asthma and influenza co-morbidity in mice

et al. 2017

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Humoral immunity serve dual functions of direct pathogen neutralization and enhancement of leukocyte function. Antibody classes are determined by antigen triggers, and the resulting antibodies can contribute to disease pathogenesis and host defense. Although asthma and influenza are immunologically distinct diseases, since we have found that allergic asthma exacerbation promotes antiviral host responses to influenza A virus, we hypothesized that humoral immunity may contribute to allergic host protection during influenza. C57BL/6J mice sensitized and challenged with Aspergillus fumigatus (or not) were infected with pandemic influenza A/CA/04/2009 virus. Negative control groups included naïve mice, and mice with only ‘asthma’ or influenza. Concentrations of antibodies were quantified by ELISA, and in situ localization of IgA- and IgE-positive cells in the lungs was determined by immunohistochemistry. The number and phenotype of B cells in spleens and mediastinal lymph nodes were determined by flow cytometry at predetermined timepoints after virus infection until viral clearance. Mucosal and systemic antibodies remained elevated in mice with asthma and influenza with prominent production of IgE and IgA compared to influenza-only controls. B cell expansion was prominent in the mediastinal lymph nodes of allergic mice during influenza where most cells produced IgG1 and IgA. Although allergy-skewed B cell responses dominated in mice with allergic airways inflammation during influenza virus infection, virus-specific antibodies were also induced. Future studies are required to identify the mechanisms involved with B cell activation and function in allergic hosts facing respiratory viral infections.

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IgM, IgG, and IgA Antibody Responses to Influenza A(H1N1)pdm09 Hemagglutinin in Infected Persons during the First Wave of the 2009 Pandemic in the United States

Cited by 33 publications

References 37 publications

Identification of novel influenza A virus exposures by an improved high‐throughput multiplex MAGPIX platform and serum adsorption

Identification of novel influenza A virus exposures by an improved high‐throughput multiplex MAGPIX platform and serum adsorption

Novel multiplex assay platforms to detect influenza A hemagglutinin subtype‐specific antibody responses for high‐throughput and in‐field applications

Humoral immune responses during asthma and influenza co-morbidity in mice

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