Induction, Persistence and Strain Specificity of Haemagglutinin-specific Secretory Antibodies in Lungs of Mice after Intragastric Administration of Inactivated Influenza Virus Vaccines

Chen, Ker-Sang; Quinnan, Gerald V.

doi:10.1099/0022-1317-69-11-2779

Cited by 33 publications

(8 citation statements)

References 14 publications

(11 reference statements)

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“…Mouse-adapted X-79 (H3N2) (A/Philippines/2/1982 (H3N2): A/Puerto Rico/8/1934 (H1N1)) virus was amplified in the lungs of 4 week-old BALB/c mice (Taconic). 43 A/Anhui/1/2013 (H7N9) was provided by the Centers for Disease Control (Atlanta, GA) and was grown in embryonated hen’s eggs. Virus stocks, nasal washes, and tissue homogenates were titrated on MDCK cells (ATCC), and virus titers were expressed as median tissue culture infectious dose (TCID 50 ).…”

Section: Methodsmentioning

confidence: 99%

Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines

et al. 2017

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The stem of the influenza A virus hemagglutinin (HA) is highly conserved and represents an attractive target for a universal influenza vaccine. The 18 HA subtypes of influenza A are phylogenetically divided into two groups, and while protection with group 1 HA stem vaccines has been demonstrated in animal models, studies on group 2 stem vaccines are limited. Thus, we engineered group 2 HA stem-immunogen (SI) vaccines targeting the epitope for the broadly neutralizing monoclonal antibody CR9114 and evaluated vaccine efficacy in mice and ferrets. Immunization induced antibodies that bound to recombinant HA protein and viral particles, and competed with CR9114 for binding to the HA stem. Mice vaccinated with H3 and H7-SI were protected from lethal homologous challenge with X-79 (H3N2) or A/Anhui/1/2013 (H7N9), and displayed moderate heterologous protection. In ferrets, H7-SI vaccination did not significantly reduce weight loss or nasal wash titers after robust 107 TCID50 H7N9 virus challenge. Epitope mapping revealed ferrets developed lower titers of antibodies that bound a narrow range of HA stem epitopes compared to mice, and this likely explains the lower efficacy in ferrets. Collectively, these findings indicate that while group 2 SI vaccines show promise, their immunogenicity and efficacy are reduced in larger outbred species, and will have to be enhanced for successful translation to a universal vaccine.

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Section: Methodsmentioning

confidence: 99%

Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines

et al. 2017

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“…The highly virulent, mouse-adapted virus A/FM/1/47-ma (H1N1) [A/FM] [67] originally provided by Earl Brown (University of Ottawa, Canada), the mouse-adapted A/Philippines/2/82 X A/PR/8/34 (H3N2) reassortant [X-79] [68], and the systemically replicating avian strain A/Vietnam/1203/2004 (H5N1) [A/VN1203] [69] have been described previously. Virus stocks were prepared as previously described [20].…”

Section: Methodsmentioning

confidence: 99%

Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses

et al. 2010

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BackgroundThe sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, “universal” vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd) expressing the conserved influenza virus antigens matrix 2 and nucleoprotein.Methodology/Principal FindingsIn BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals.Conclusion/SignificanceMucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.

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“…However, when in the latter study CTB was substituted by the holotoxin local and systemic antibodies were induced (Liang et al, 1988;Nedrud et al, 1987). Successful oral immunization has also been achieved with sonicated Helicobacter pylori and the cholera holotoxin in outbred Swiss mice (Czinn et al, 1993) or with inactivated influenza virus and the heatlabile enterotoxin of E. coli in BALB/c mice (LT; Chen & Quinnan, 1988). Even in the presence of the LT holotoxin (Clements et al, 1988), intragastric MV was unable to elicit antibodies detectable by ELISA or Western blot.…”

Section: Discussionmentioning

confidence: 99%

Cholera toxin B stimulates systemic neutralizing antibodies after intranasal co-immunization with measles virus

Beauverger¹,

Schneider²,

Jung³

et al. 1995

Journal of General Virology

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An effÉcient mucosal vaccination has a number of obvious advantages over invasive routes of immunization. The immune response to measles virus (MV) was investigated after intranasal and intragastric coimmunization of mice with cholera toxin B (CTB) as an adjuvant. High titres of virus-specific IgG antibodies and a transient IgA response were detected in the sera after intranasal but not after intragastric immunization when CTB was used. In the presence of CTB, higher titres were reached with less antigen and fewer intranasal boosts. Neutralizing antibodies were found in all animals only after co-immunization with MV and CTB. In the nasal wash and the saliva, IgG and IgA titres were significant only in the MV plus CTB groups; IgG levels were comparable to those found after intraperitoneal (i.p.) immunization with complete Freund's adjuvant. Specific IgA was detected in the mucosal fluids only after intranasal immunization with MV plus CTB but not after i.p. or intragastric immunization. The antibody response consisted of 99 % IgG1 after MV immunization. In the CTB groups 10% IgG2b and 1% IgG2a were detected in addition to the predominant IgG1 antibodies.

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Induction, Persistence and Strain Specificity of Haemagglutinin-specific Secretory Antibodies in Lungs of Mice after Intragastric Administration of Inactivated Influenza Virus Vaccines

Cited by 33 publications

References 14 publications

Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines

Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines

Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses

Cholera toxin B stimulates systemic neutralizing antibodies after intranasal co-immunization with measles virus

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