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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2005 May 14

PMID 15890902

Citations 56

Authors

Darya Zharikova

Krystyna Mozdzanowska

Jingqi Feng

Manxin Zhang

Walter Gerhard

Affiliations

Soon will be listed here.

Abstract

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.

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