B cell responses to H5 influenza HA in human subjects vaccinated with a drifted variant

Baer, Jane; Santiago, Felix W.; Yang, Hongmei; Wu, Hulin; Holden‐Wiltse, Jeanne; Treanor, John J.; Topham, David J.

doi:10.1016/j.vaccine.2009.11.002

Cited by 18 publications

(21 citation statements)

References 52 publications

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“…We selected an elderly population and specifically focused on influenza A/H1N1-specific memory B cells. Our data support the conclusion that the B cell ELISPOT assay is a highly effective method to detect influenza A/H1N1-specific B cells after vaccination (1,12,23). Several strains of the influenza virus exist due to the known variances in the HA and NA surface antigens.…”

Section: Discussionsupporting

confidence: 87%

“…Therefore, coating the plates with recombinant H1 viral glycoprotein instead of whole influenza virus would exclusively detect H1-specific B cells, thus measuring the B cell response against the major viral surface protective antigenthe hemagglutinin. This type of assay is observed in the work of Baer et al, who optimized a B cell ELISPOT detection of influenza-specific H5-specific B cells (1). However, the H1 protein is the primary surface antigen known for initial cellular interaction, and neuraminidase (N1) is responsible for the hydrolysis of the sialic acid-H1 complex for viral release.…”

Section: Discussionmentioning

confidence: 99%

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Detection of Influenza A/H1N1-Specific Human IgG-Secreting B Cells in Older Adults by ELISPOT Assay

et al. 2014

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B cells play an important role in humoral immunity and antibody production. Use of a B cell ELISPOT assay to quantify antigen-specific B cells can assist other assays to achieve a more complete profile of the humoral immune response after vaccination. We utilized a B cell ELISPOT assay to measure the number of influenza A/H1N1-specific B cells at key timepoints after seasonal influenza vaccination in 106 older adults (50-74 years of age). Blood was drawn from these subjects on Day 0, Day 3, Day 28, and Day 75 after vaccination to represent baseline, early, peak, and late response, respectively, of influenza A/H1N1-specific B cells. A significant increase in A/H1N1-specific B cells (median 36 spot-forming units/SFUs per 200,000 cells, p < 0.0001) was seen on Day 28 compared to baseline and Day 3, and this number decreased (23 SFUs, p < 0.0001) by Day 75, but not to baseline level. These data suggest that the B cell ELISPOT can be used to profile and monitor the humoral immune responses in older subjects after influenza vaccination, and serve as an immune signature marker.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Detection of Influenza A/H1N1-Specific Human IgG-Secreting B Cells in Older Adults by ELISPOT Assay

et al. 2014

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“…Previous reports from human studies have shown that prior immunization with an rH5 HA (A/Hong Kong/156/97) vaccine results in a “boosted” response to the drift variant VN04 upon re-vaccination with a single dose of A/VN/1203/04 split vaccine [20, 21]. To study how prior immunity to H5 HA can influence the antibody response elicited upon vaccination with rHA derived from a different H5 virus clade, an immunization schedule that included a drifted variant of rH5 HA was developed (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Evidence supporting the idea of pre-vaccination is limited, but studies in humans suggest that immunization with baculovirus-expressed recombinant hemagglutinin (rHA) H5N1 vaccine (clade 0) primes the immune system, resulting in clinically significant serological responses following a single dose of a inactivated H5N1 vaccine containing a drifted (clade 1) virus [20]. Further studies, using the same cohort of subjects, have revealed that there is a population of memory B cells that are specific and cross-reactive to both H5 HA antigens and respond rapidly to vaccination with the drifted variant [21]. These studies show that pre-vaccination does not preclude the ability to generate new and/or cross-reactive cellular and antibody responses to the new drifted H5.…”

Section: Introductionmentioning

confidence: 99%

Vaccination with drifted variants of avian H5 hemagglutinin protein elicits a broadened antibody response that is protective against challenge with homologous or drifted live H5 influenza virus

Santiago¹,

Fitzgerald²,

Treanor³

et al. 2011

Vaccine

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Substantial H5 influenza HA directed immunity is elicited after vaccination of human subjects who had been previously immunized with a drifted H5 HA variant. We sought to investigate the characteristics of H5 HA specific immune responses in more depth by developing an animal model of H5 HA vaccination using drift variants of recombinant H5 HA proteins. HA proteins derived from influenzas A/Vietnam/1203/04 (Clade 1) and A/Indonesia/05/05 (Clade 2.1) were chosen. The sequence of vaccination consisted of two doses of homologous protein, followed by one additional dose of the homologous or heterologous, drifted HA protein. Each dose of HA was combined with CpG as an adjuvant and was injected subcutaneously. All the animals exhibited a serum IgG antibody response that cross-reacted with both HAs in an ELISA. However, those animals that received the drifted variant exhibited higher reactivity to the heterologous HA. Competitive ELISA of serum from drift-variant recipients showed evidence of antibody focusing towards the drifted HA, suggesting modification of the response towards improved cross-reactivity, though development of neutralizing antibodies was limited. Nevertheless, animals were protected against live-virus challenge, and passive transfer of serum was sufficient to confer protection to otherwise naïve mice, indicating that both neutralizing and non-neutralizing antibodies offer some degree of protection. These findings suggest that pre-vaccination against H5 influenza has the potential to prime immunity against emerging drifted H5 strains, and could also lower the dose requirements of vaccination in the event of a pandemic.

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“…Both animal models and human studies which make use of peripheral blood mononuclear cell (PBMC) sampling have long been used to study the immune response to influenza infection (Baer et al, 2010; Falsey et al, 2009; Halliley et al, 2010). Animal models have some advantages over human studies, including high frequency sampling of multiple tissues (Miao et al, 2010) and the ability to block or deplete individual immune response elements such as the CD8 effector and B cell mediated antibody responses (Teijaro et al, 2010; Zeng et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Quantifying Immune Response to Influenza Virus Infection via Multivariate Nonlinear ODE Models with Partially Observed State Variables and Time-Varying Parameters

Miao

Han

et al. 2014

Stat Biosci

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Summary Influenza A virus (IAV) infection continues to be a global health threat, as evidenced by the outbreak of the novel A/California/7/2009 IAV strain. Previous flu vaccines have proven less effective than hoped for emerging IAV strains, indicating a more thorough understanding of immune responses to primary infection is needed. One issue is the difficulty in directly measuring many key parameters and variables of the immune response. To address these issues, we considered a comprehensive workflow for statistical inference for ordinary differential question (ODE) models with partially observed variables and time-varying parameters, including identifiability analysis, two-stage and NLS estimation, and model selection etc‥ In particular, we proposed a novel one-step method to verify parameter identifiability and formulate estimating equations simultaneously. Thus, the pseudo-LS method can now deal with general ODE models with partially observed state variables for the first time. Using this workflow, we verified the relative significance of various immune factors to virus control, including target epithelial cells, cytotoxic T-lymphocyte (CD8+) cells and IAV specific antibodies (IgG and IgM). Factors other than cytotoxic T-lymphocyte (CTL) killing contributed the most to the loss of infected epithelial cells, though the effects of CTL are still significant. IgM antibody was found to be the major contributor to neutralization of free infectious viral particles. Also, the maximum viral load, which correlates well with mortality, was found to depend more on viral replication rates than infectivity. In contrast to current hypotheses, the results obtained via our methods suggest that IgM antibody and viral replication rates may be worth of further explorations in vaccine development.

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B cell responses to H5 influenza HA in human subjects vaccinated with a drifted variant

Cited by 18 publications

References 52 publications

Detection of Influenza A/H1N1-Specific Human IgG-Secreting B Cells in Older Adults by ELISPOT Assay

Detection of Influenza A/H1N1-Specific Human IgG-Secreting B Cells in Older Adults by ELISPOT Assay

Vaccination with drifted variants of avian H5 hemagglutinin protein elicits a broadened antibody response that is protective against challenge with homologous or drifted live H5 influenza virus

Quantifying Immune Response to Influenza Virus Infection via Multivariate Nonlinear ODE Models with Partially Observed State Variables and Time-Varying Parameters

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