An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus

Leung, Ho-chuen; Chan, Chris; Poon, Vincent Kwok-Man; Zhao, Hanjun; Cheung, Chi-Wai; Ng, Fai; Huang, Jian‐Dong; Zheng, Bo‐Jian

doi:10.1038/emi.2015.22

Cited by 19 publications

(13 citation statements)

References 34 publications

(49 reference statements)

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“…10 Interestingly, a B-cell epitope in M2e includes this range of aa 7-17, but it appears that differences in aa at certain positions 13, 14, or 18 between different strains do not markedly affect the protective efficacy of M2e immunization, whereas mutations in aa 10, 11, or 16 reduce the antibody-binding affinity. [85][86][87] Considering that M2e-specific CD4 T cells are also protective, some earlier attempts at correlating protective efficacy following M2e immunization to antibody-binding specificities exclusively may have to be revisited. A recently published report from the World Health Organization Product Development for Vaccines Advisory Committee identified 41 universal influenza vaccine candidates at various stages of development; a list that includes our own CTA1-3M2e-DD.…”

Section: Discussionmentioning

confidence: 99%

M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection

et al. 2018

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Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection. Indeed, immunized IL-17A mice were significantly less well protected compared with wild-type mice despite exhibiting comparable antibody levels. Similarly, poor protection was also observed in congenic Balb/B (H-2) mice, which failed to develop M2e-specific CD4 T cells, but exhibited comparable antibody levels. Lung-resident CD69 CD103 M2e-specific memory CD4 T cells were αβ TCR and 50% were Th17 cells that were associated with an early influx of neutrophils after virus challenge. Adoptively transferred M2e memory CD4 T cells were strong helper T cells, which accelerated M2e- but more importantly also hemagglutinin-specific IgG production. Thus, for the first time we demonstrate that M2e-specific memory CD4 T cells are broadly protective.

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Section: Discussionmentioning

confidence: 99%

M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection

et al. 2018

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“…We have also demonstrated the ability of a recombinant fusion protein (M2e3-ASP-1) containing three conserved H5N1 M2e molecules and a new Onchocerca volvulus activation associated protein-1 (ASP-1) adjuvant in cross-protection against two divergent strains of H5N1 influenza viruses [25]. In addition, H5N1 M2e peptide-based vaccines were developed to test the cross-protection of H5N1 M2e against infection of the new H7N9 virus, and the H5N1 M2e vaccination provided potent cross-protection against lethal challenge of H7N9 virus [37,38]. In this study, we designed two recombinant universal influenza vaccines by respectively linking two molecules of M2e and one molecule of HA-FP sequences of H5N1 and H7N9 in two different orders, and evaluated their immunogenicity and protection against a heterologous H1N1 strain.…”

Section: Discussionmentioning

confidence: 99%

Highly conserved M2e and hemagglutinin epitope-based recombinant proteins induce protection against influenza virus infection

Guo

Song

et al. 2017

Microbes and Infection

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Highly pathogenic influenza viruses continue to cause serious threat to public health due to their pandemic potential, calling for an urgent need to develop effective, safe, convenient, and universal vaccines against influenza virus infection. In this study, we constructed two recombinant protein vaccines, 2H5M2e-2H7M2e-H5FP-H7FP (hereinafter M2e-FP-1) and 2H5M2e-H5FP-2H7M2e-H7FP (hereinafter M2e-FP-2), by respectively linking highly conserved sequences of two molecules of ectodomain of M2 (M2e) and one molecule of fusion peptide (FP) epitope of hemagglutinin (HA) of H5N1 and H7N9 influenza viruses in different orders. The Escherichia coli-expressed M2e-FP-1 and M2e-FP-2 proteins induced similarly high-titer M2e-FP-specific antibodies in the immunized mice. Importantly, both proteins were able to prevent lethal challenge of heterologous H1N1 influenza virus, with significantly reduced viral titers and alleviated pathological changes in the lungs, as well as increased body weight and complete survivals, in the challenge mice. Taken together, our study demonstrates that highly conserved M2e and FP epitope of HA of H5N1 and H7N9 influenza viruses can be used as important targets for development of safe and economical universal influenza vaccines, and that the position of H7N9 M2e and H5N1 HA epitope sequences in the vaccine components has no significant effects on the immunogenicity and efficacy of M2e-FP-based subunit vaccines.

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“…Leung H.-C. с соавт. продемонстрировали способность пептида, представляющего со-бой М2е-тетрамер от вируса гриппа А H5N1 (H5N1-M2e), индуцировать защиту у мышей как против гомологичного подтипа H5N1, так и против гетерологичных подтипов H1N1 и H7N9 [55]. В частности в последней работе было показано, что иммунизация H5N1-M2e в сочетании с адъювантом Фрейнда или адъ-ювантной системой Sigma на 80% защищает мышей от заражения 10ЛД 50 вируса гриппа A/ Anhui/01/13 (H7N9) и предотвращает повреж-дения тканей легких [55].…”

Section: кандидатные вакцины на основе м2еunclassified

“…продемонстрировали способность пептида, представляющего со-бой М2е-тетрамер от вируса гриппа А H5N1 (H5N1-M2e), индуцировать защиту у мышей как против гомологичного подтипа H5N1, так и против гетерологичных подтипов H1N1 и H7N9 [55]. В частности в последней работе было показано, что иммунизация H5N1-M2e в сочетании с адъювантом Фрейнда или адъ-ювантной системой Sigma на 80% защищает мышей от заражения 10ЛД 50 вируса гриппа A/ Anhui/01/13 (H7N9) и предотвращает повреж-дения тканей легких [55]. Так же, как было опи-сано в предыдущей главе, иммуногенностью и протективностью против различных под-типов вируса гриппа А, обладает кандидатная рекомбинантная вакцина на основе бактерии Lactobacillus casei, экспрессирующей на поверх-ности белок М2, лишенный трансмембранно-го домена (sM2), фрагмент стволовой части НА и субъединицу холерного токсина А1 (pgsACTA1sM2HA2/L.…”

Section: кандидатные вакцины на основе м2еunclassified

“…Так же, как было опи-сано в предыдущей главе, иммуногенностью и протективностью против различных под-типов вируса гриппа А, обладает кандидатная рекомбинантная вакцина на основе бактерии Lactobacillus casei, экспрессирующей на поверх-ности белок М2, лишенный трансмембранно-го домена (sM2), фрагмент стволовой части НА и субъединицу холерного токсина А1 (pgsACTA1sM2HA2/L. casei) [55]. Имеются данные о том, что введение мышам 15 мкг рекомби-нантного белка М2, лишенного трансмем-бранного домена, в сочетании с адьювантом цитозаном обеспечивает 100%-ную защиту от гомологичного штамма, 90%-ную защиту от гетерологичного штамма H1N1 и 30%-ную защиту от гетерологичного штамма H5N1 [85].…”

Section: кандидатные вакцины на основе м2еunclassified

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Current Approaches to Universal Vaccine Against Influenza Virus

Булатович

Alekseeva

Саядян

et al. 2016

Russian Journal of Infection and Immunity

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Influenza is a seasonal infectious disease widespread across the globe. In Russia the share of influenza and other acute respiratory viral infections account for up to 90% of all infectious diseases. Scientific and reasonable method of influenza prevention is vaccination. However, traditional current influenza vaccines can’t induce protection against various virus strains that differ substantially in terms of their antigenic structure, and thus require periodic updates to its immunogenic components. In addition, there is the risk of a pandemic caused by an entirely new antigen in relation to variants of influenza virus A. Attempts to improve on traditional approaches to vaccination have focused primarily on improving production technologies and to increase immunogenicity of vaccines. Therefore, the urgent task is the creation of vaccines able to induce immune response a broad spectrum against different influenza virus strains and human strains of avian influenza, also can cause disease in humans. Protective effect of universal vaccine should be the induction of integrated immune response, based on the formulation of cross-reactive antibodies and T cells. The development of such universal vaccine could remove the need for periodical strain composition update of existing vaccines and, accor dingly, will be able to give the vaccine manufacturer itself, production planning regardless of epidemic seasons. Currently, the most widely studied antigens as key components of flu vaccines are proteins M2 and NP as well as the hemagglutinin of influenza virus. This review summarizes and lists some data of domestic and foreign research on a universal influenza virus vaccine.

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An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus

Cited by 19 publications

References 34 publications

M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection

M2e-tetramer-specific memory CD4 T cells are broadly protective against influenza infection

Highly conserved M2e and hemagglutinin epitope-based recombinant proteins induce protection against influenza virus infection

Current Approaches to Universal Vaccine Against Influenza Virus

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