H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

Howard, M. Keith; Sabarth, Nicolas; Savidis-Dacho, Helga; Portsmouth, Daniel; Kistner, Otfried; Kreil, Thomas R.; Ehrlich, Hartmut J.; Barrett, Perry

doi:10.1371/journal.pone.0023791

Cited by 19 publications

(14 citation statements)

References 43 publications

(48 reference statements)

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“…2). A previous study demonstrated that a minimum neutralizing antibody concentration with a 1:16 endpoint titer is sufficient to provide complete protection against H5N1 viruses (38). Although antibody-mediated protection is suggested to be the main contributor of protection in our vaccine, T cells may also play a role.…”

Section: Discussionmentioning

confidence: 92%

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Kamlangdee

Kingstad-Bakke

Anderson

et al. 2014

J Virol

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A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4 ؉ and CD8 ؉ T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity. IMPORTANCEInfluenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel in silico mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent Tcell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.

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Section: Discussionmentioning

confidence: 92%

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Kamlangdee

Kingstad-Bakke

Anderson

et al. 2014

J Virol

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“…For the MN assay, no standardized assay and no internationally accepted cutoff for seroprotection exists. The seroprotection MN titer cutoff of 1:20 is based on the previously demonstrated statistically significant correlation with the SRH area of 25 mm 2 (5) and validation in passive transfer challenge studies in mice (24). Licensure of the whole-virus H5N1 vaccine was granted by the European regulatory authorities based on data obtained using these validated MN and SRH assays (25,26).…”

Section: Methodsmentioning

confidence: 99%

Safety and Immunogenicity of a Vero Cell Culture-Derived Whole-Virus H5N1 Influenza Vaccine in Chronically Ill and Immunocompromised Patients

Velden

Geisberger

Dvorak

et al. 2014

Clin Vaccine Immunol

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“…NT antibodies in serum samples are usually assessed by means of the microneutralization (MN), either CPE (cytopathic effect)‐based or ELISA‐based, or the plaque‐reduction neutralization (PRNT) assay. In the present review, we focused on the CPE‐based MN assay, since this is the preferred method because of its simplicity of execution, its ability to evaluate large numbers of samples, and the standardization of the quantity of virus used in the assay . Along with the ELISA sIgA assay, the MN assay constitutes a valid approach to evaluate the immunogenicity of LAIVs, IIVs, or recombinant influenza vaccines (eg rHA) in inducing selective anti‐influenza antibodies with influenza virus–neutralizing potential.…”

Section: Neutralizing (Nt) Antibodies In Nasal Wash/swab and Future Amentioning

confidence: 99%

How to assess the effectiveness of nasal influenza vaccines? Role and measurement of sIgA in mucosal secretions

Gianchecchi

Manenti

Kistner

et al. 2019

Influenza Resp Viruses

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Secretory IgAs (sIgA) constitute the principal isotype of antibodies present in nasal and mucosal secretions. They are secreted by plasma cells adjacent to the mucosal epithelial cells, the site where infection occurs, and are the main humoral mediator of mucosal immunity. Mucosally delivered vaccines, such as live attenuated influenza vaccine (LAIV), are able to mimic natural infection without causing disease or virus transmission and mainly elicit a local immune response. The measurement of sIgA concentrations in nasal swab/wash and saliva samples is therefore a valuable tool for evaluating their role in the effectiveness of such vaccines. Here, we describe two standardized assays (enzyme‐linked immunosorbent assay and microneutralization) available for the quantification of sIgA and discuss the advantages and limitations of their use.

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H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

Cited by 19 publications

References 43 publications

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Safety and Immunogenicity of a Vero Cell Culture-Derived Whole-Virus H5N1 Influenza Vaccine in Chronically Ill and Immunocompromised Patients

How to assess the effectiveness of nasal influenza vaccines? Role and measurement of sIgA in mucosal secretions

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