Tandem repeats of the extracellular domain of Matrix 2 influenza protein exposed in Brucella lumazine synthase decameric carrier molecule induce protection in mice

Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses

“…Based on previous studies, we knew that adjuvanted, single or tandem M2e repeats elicit strong serum IgG and mucosal IgA antibody responses. [26][27][28] These studies also established that 3-4 M2e repeats in tandem improved humoral immunity over the use of a single M2e, and that immunization with tandem M2e repeats induce protection against a broad range of influenza virus subtypes. Thus, in this work, we incorporated 3 tandem M2e sequences from 3 different viruses.…”

“…33 Moreover, immunization with HA2 provides for faster elimination of influenza virus in mouse lung and increases survival rates. 34 Although anti-M2e antibody is not able to neutralize the virus to prevent virus entry, it is able to disrupt the virus life cycle [26][27][28] and promotes death of infected cells by antibody-dependent cell-mediated cytotoxicity. 35,36 We performed cross-neutralization assays using sera from mice immunized with CTB-3 × M2e-HA2 and PR8 influenza virus in vitro, and similar to those studies performed with HA2 and M2e antigens, CTB-3 × M2e-HA2 immune sera lacked virus neutralization activity against PR8 and CA09 influenza viruses (data not shown).…”

Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate

“…Several strategies were reported in an attempt to overcome poor immunogenicity of M2e, including fusion of M2e peptides to immunogenic carrier proteins(De Filette et al, 2005; Fan et al, 2004; Neirynck et al, 1999) with some adjuvants or delivery of VLPs containing M2e epitopes (Alvarez et al, 2013; Bessa et al, 2008; Hashemi et al, 2012; Jegerlehner et al, 2004; Kim et al, 2013b; Turley et al, 2011). A prevous study reported that HA2 stalk domain-based vaccines conferred survial protection in vaccinated mice after challenge (Steel et al, 2010).…”

Advancements in the development of subunit influenza vaccines

“…With this vaccination strategy, protein carriers themselves have potential adjuvanticity, thus avoiding the use of strong adjuvants or additional adjuvants during immunization [74, 75], a step which simplifies the immunization process, but achieves similar immune effects. Therefore, this vaccination strategy is more practical, representing a future direction for the development of M2e-based universal subunit vaccines.…”

“…Therefore, this vaccination strategy is more practical, representing a future direction for the development of M2e-based universal subunit vaccines. Studies have also demonstrated that fusion of four tandem copies of M2e molecules with the immunogenic decameric protein Brucella abortus lumazine synthase, BLS-4M2e, resulted in survival rates of 100% and 80% for mice challenged with influenza virus in the presence of Iscomatrix or alum adjuvant, respectively, while 60% of these mice still survived in the absence of such adjuvants [75]. We have also found that a recombinant fusion protein linking three tandem copies of the H5N1 M2e consensus sequence to activation associated protein-1 (ASP-1) adjuvant (M2e3-ASP-1) was able to provide significant M2e-specific immune responses and cross-clade protective immunity against divergent H5N1 viruses without the requirement of additional adjuvants [76].…”