Antibody response to the M2 protein of influenza A virus expressed in insect cells

Black, Renee A.; Rota, Paul A.; Gorodkova, Natalia; Klenk, Hans‐Dieter; Kendal, Alan P.

doi:10.1099/0022-1317-74-1-143

Cited by 124 publications

(69 citation statements)

References 24 publications

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“…An additional factor that may contribute to the low degree of change seen in M2e among human influenza virus strains could be the absence of M2e-specific Abs and thus pressure for change. A small study of 17 paired human sera obtained during the acute and convalescent phase of natural infection found that M2-specific Abs were absent from acute-phase sera and became detectable by enzyme-linked immunosorbent assay (ELISA) in only six of the convalescents (3). This was in contrast to nucleoprotein-specific Ab titers, which increased in 15 of 17 convalescent-phase sera, thus confirming recent influenza virus infection of the donors (3).…”

mentioning

confidence: 52%

“…This could be because M2e-specific Abs, if present, do not restrict virus growth in humans, as reported recently for pigs (10). More likely, the absence of these mutations among human epidemic strains is a reflection of the poor M2e-specific Ab response in humans, as indicated by two previous studies (3,18). Further analyses of the M2e-specific Ab response in humans are likely to provide more insight into this important issue.…”

Section: Vol 79 2005 Matrix Protein 2 Escape Mutants 6649mentioning

confidence: 88%

“…Hybridoma-SFM is serum-free medium from Invitrogen. PBSN is phosphate-buffered saline (PBS; pH 7.2) containing 3 mM NaN 3 .…”

Section: Vol 79 2005 Matrix Protein 2 Escape Mutants 6645mentioning

confidence: 99%

“…A small study of 17 paired human sera obtained during the acute and convalescent phase of natural infection found that M2-specific Abs were absent from acute-phase sera and became detectable by enzyme-linked immunosorbent assay (ELISA) in only six of the convalescents (3). This was in contrast to nucleoprotein-specific Ab titers, which increased in 15 of 17 convalescent-phase sera, thus confirming recent influenza virus infection of the donors (3). Another study found no difference in M2e-specific Ab titers in two larger groups of unpaired sera, one positive and the other negative for virus-specific Abs (18).…”

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confidence: 99%

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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

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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mentioning

confidence: 52%

Section: Vol 79 2005 Matrix Protein 2 Escape Mutants 6649mentioning

confidence: 88%

“…Hybridoma-SFM is serum-free medium from Invitrogen. PBSN is phosphate-buffered saline (PBS; pH 7.2) containing 3 mM NaN 3 .…”

Section: Vol 79 2005 Matrix Protein 2 Escape Mutants 6645mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

106

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“…• Following infection or vaccination with inactivated, licensed influenza vaccines, serum antibody levels specific for M2e are low in humans, pigs and mouse [33][34][35][36][37]. A presumptive HLA-B27 and HLA-B44 restricted human cytotoxic T-lymphocyte epitope has been identified in M2e, but its contribution to protection against influenza in the human population, if any, is unknown [38][39][40].…”

Section: Why Is M2e Conserved?mentioning

confidence: 99%

The Influenza Matrix Protein 2 as a Vaccine Target

Saelens

2008

Future Virol.

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Matrix protein (M)2 is an Influenza A, type III membrane protein with an extracellular domain (ectodomain of M2 [M2e]) of 23 amino acid residues, which is strongly conserved across virus strains. M2 fulfills an important biological function in the life cycle of the Influenza A virus and has been a target of antiviral drugs. M2e has generated much interest as a potential vaccine target, and a clinical M2e vaccine trial was initiated in 2007. The advantage of M2e compared with hemagglutinin, the prime antigen target in conventional influenza vaccines, is that its sequence is conserved. This means that a stable, efficacious and easily produced M2e-based vaccine would provide protection not only against drifting seasonal influenza epidemic strains, but would also make it possible to vaccinate in anticipation of an emerging pandemic. Furthermore, most reported M2e-based vaccines are produced by economical and safe technologies. IgG subtype antibodies directed against M2e can prevent death from influenza and reduce morbidity in animal models for influenza disease. The immunological mechanism that mediates protection by anti-M2e antibodies is not completely understood, but it probably involves antibody-mediated cellular cytotoxicity. This review summarizes the findings on M2e vaccine candidates and addresses some of the key unanswered questions about this promising Influenza A vaccine target: what is its likely mechanism of action? Which measurable parameters correlate with protection? And what can be expected from clinical use of an M2e-based vaccine?

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