Treatment of Influenza Virus-Infected SCID Mice with Nonneutralizing Antibodies Specific for the Transmembrane Proteins Matrix 2 and Neuraminidase Reduces the Pulmonary Virus Titer but Fails to Clear the Infection

Mozdzanowska, Krystyna; Maiese, Krista; Furchner, Michelle; Gerhard, Walter

doi:10.1006/viro.1998.9534

Cited by 110 publications

(109 citation statements)

References 52 publications

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“…This is in line with the requirement for Th1 cytokine responses, such as IFN-g for Ig class switching and associated enhancement of cellular antiviral responses (22)(23)(24). This is further confirmed by the observation that a subtype switch from IgG1 anti-M2e monoclonal 14C2 to the switch variant anti-M2e IgG2a improves its protective efficacy in vivo (17,25).…”

supporting

confidence: 69%

“…Indeed, protective immunity can be transferred from vaccinated animals to naive recipients by serum (11,(13)(14)(15)(16). Moreover, anti-M2e mAbs protect wild-type and immunodeficient scid recipient mice against influenza A virus infection (17)(18)(19). Although a contribution by M2e-specific T cell responses to protection cannot be ruled out, M2e-specific serum Abs are crucial for immune protection.…”

mentioning

confidence: 99%

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Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection

Bakkouri

Descamps

Filette

et al. 2011

The Journal of Immunology

300

263

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The ectodomain of matrix protein 2 (M2e) of influenza A virus is an attractive target for a universal influenza A vaccine: the M2e sequence is highly conserved across influenza virus subtypes, and induced humoral anti-M2e immunity protects against a lethal influenza virus challenge in animal models. Clinical phase I studies with M2e vaccine candidates have been completed. However, the in vivo mechanism of immune protection induced by M2e-carrier vaccination is unclear.

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supporting

confidence: 69%

mentioning

confidence: 99%

Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection

Bakkouri

Descamps

Filette

et al. 2011

The Journal of Immunology

300

263

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“…Unlike HA-specific Abs (22,25), M2e-specific Abs cannot prevent virus from initiating an infection or resolve an established infection, but they can diminish the yield of infectious virus and thus inhibit progression of the infection (23,31). We were interested in establishing an experimental system in which the growth-restricting activity of M2e-specific Ab and the capability of influenza virus to escape it could be best assessed in vivo.…”

Section: Progression Of a Nasal Pr8 Virus Infection In Scid Micementioning

confidence: 99%

“…Indeed, the majority of human epidemic strains isolated since 1918 share the same M2e protein sequence. Second, several studies in mice have shown that M2e-specific Abs restrict influenza virus replication and reduce morbidity and mortality (6,19,23,24,31). Furthermore, a recent study in ferrets, the animal model considered most prognostic for human influenza, has demonstrated protective activity of M2e-specific immunity (6), and sera from rhesus monkeys immunized with a M2e-carrier conjugate have been shown to exhibit protective activity upon transfer into mice (6).…”

mentioning

confidence: 99%

Influenza Type A Virus Escape Mutants Emerge In Vivo in the Presence of Antibodies to the Ectodomain of Matrix Protein 2

Zharikova

Mozdzanowska

Feng

et al. 2005

J Virol

Self Cite

106

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The ectodomain of matrix protein 2 (M2e) of human influenza type A virus strains has remained remarkably conserved since 1918. Because M2e-specific immunity has been shown to decrease morbidity and mortality associated with influenza virus infection in several animal models and because natural infection and current vaccines do not appear to induce a good M2e-specific antibody (Ab) response, M2e has been considered as potential vaccine for inducing cross-reactive protection against influenza type A viruses. The high degree of structural conservation of M2e could in part be the consequence of a poor M2e-specific Ab response and thus the absence of pressure for change. To assess this possibility, we studied the course of infection in SCID mice in the presence or absence of passive M2e-specific monoclonal Abs (MAbs). We found that virus mutants with antigenic changes in M2e emerged in 65% of virus-infected mice treated with M2e-specific but not control MAbs. However, the diversity of escape mutants was highly restricted since only two types were isolated from 22 mice, one with a proline-to-leucine and the other with a proline-to-histidine interchange at amino acid position 10 of M2e. The implications of these findings for the use of M2e as a broadly protective vaccine are discussed.Current influenza virus vaccines aim to induce strong antibody (Ab) responses to the ectodomains of hemagglutinin (HA) and neuraminidase (NA) molecules, since these antibodies (Abs) can provide potent protection against infection and/or disease. The main deficiency of this protection is that it targets highly variable viral determinants. This necessitates not only frequent updating of the vaccine to contemporary circulating virus strains but, given that vaccines have to be produced and applied ahead of exposure to epidemic strains, also a correct prediction of these future epidemic strains. Failure to anticipate the emergence of an epidemic strain with significant antigenic changes compared to the vaccine strain will greatly reduce vaccine-induced protection. It would be advantageous, therefore, to expand vaccine-mediated protection to less variable viral targets. One possible way to achieve this may be through induction of 9,10,14,18,21,24,28).M2 is a 97-amino-acid transmembrane protein of influenza type A virus (15, 16). The mature protein forms homotetramers (12, 29) that have pH-inducible ion channel activity (27,29). M2-tetramers are expressed at high density in the plasma membrane of infected cells but are relatively excluded from sites of virus maturation and therefore incorporated only at low frequency into the membrane of mature virus particles (30,33). Most important in the present context are, first, that the sequence of the 24-amino-acid ectodomain of M2 (M2e) has remained remarkably conserved among human epidemic virus strains (Fig. 1A) (20). Indeed, the majority of human epidemic strains isolated since 1918 share the same M2e protein sequence. Second, several studies in mice have shown that M2e-specific Abs restrict influenz...

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“…However, antibodies raised against non-HI epitopes or other viral proteins [20][21][22][23], as well as cell mediated immunity (CMI) (reviewed in [24]), clearly play a role in the heterologous cross-reactive immune responses (Het-I) against influenza virus infection. Exposure to live virus or MLV vaccine is likely to have a more robust response against many viral epitopes through heightened cell-mediated immune activation and through the induction of mucosal immunity.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

Vincent

Lager

et al. 2007

Vaccine

133

127

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In the U.S., despite available swine influenza virus (SIV) vaccines, multiple influenza subtypes as well as antigenic and genetic variants within subtypes continue to circulate in the swine population. One of the challenges to control and eliminate SIV is that the currently used inactivated influenza virus vaccines do not provide adequate cross-protection against multiple antigenic variants of SIV in the field. We previously generated a recombinant H3N2 swine influenza virus (SIV) based on the influenza A/SW/TX/4199-2/98 virus (TX98) containing an NS1 gene expressing a truncated NS1 protein of 126 amino acids, TX98-NS1Δ126 virus. This recombinant strain was demonstrated to be highly attenuated in swine and showed potential for use as a modified live-virus vaccine (MLV) after intratracheal application in pigs. However, this route of inoculation is not practical for vaccination in the field. In the present study, we first compared intramuscular and intranasal routes of application of the MLV, and found that the intranasal route was superior in priming the local (mucosal) immune response. Pigs were then vaccinated via the intranasal route and challenged with wild type homologous TX98 H3N2 virus, with a genetic and antigenic variant H3N2 SIV (influenza A/SW/ CO/23619/99 virus, CO99) and a heterosubtypic H1N1 SIV (influenza A/SW/IA/00239/2004 virus, IA04). The intranasally vaccinated pigs were completely protected against homologous challenge. In addition, MLV vaccination provided nearly complete protection against the antigenic H3N2 variant CO99 virus. When challenged with the H1N1 IA04 virus, MLV vaccinated animals displayed reduced fever and virus titers despite minimal reduction in lung lesions. In vaccinated pigs, there was no serologic cross-reactivity by HI assays with the heterologous or heterosubtypic viruses. However, there appeared to be substantial cross-reactivity in antibodies at the mucosal level with the CO99 virus in MLV vaccinated pigs.

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Treatment of Influenza Virus-Infected SCID Mice with Nonneutralizing Antibodies Specific for the Transmembrane Proteins Matrix 2 and Neuraminidase Reduces the Pulmonary Virus Titer but Fails to Clear the Infection

Cited by 110 publications

References 52 publications

Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection

Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection

Influenza Type A Virus Escape Mutants Emerge In Vivo in the Presence of Antibodies to the Ectodomain of Matrix Protein 2

Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

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