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Article

Generation and Characterization of Universal Live-Attenuated Influenza Vaccine Candidates Containing Multiple M2e Epitopes

1
Department of Virology, Institute of Experimental Medicine, Saint Petersburg 197376, Russia
2
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(4), 648; https://doi.org/10.3390/vaccines8040648
Received: 2 October 2020 / Revised: 20 October 2020 / Accepted: 29 October 2020 / Published: 3 November 2020
(This article belongs to the Special Issue Advances in Vaccine Development and Immunotherapies)
Influenza viruses constantly evolve, reducing the overall protective effect of routine vaccination campaigns. Many different strategies are being explored to design universal influenza vaccines capable of protecting against evolutionary diverged viruses. The ectodomain of influenza A M2e protein (M2e) is among the most promising targets for universal vaccine design. Here, we generated two recombinant live attenuated influenza vaccines (LAIVs) expressing additional four M2e tandem repeats (4M2e) from the N-terminus of the viral hemagglutinin (HA) protein, in an attempt to enhance the M2e-mediated cross-protection. The recombinant H1N1+4M2e and H3N2+4M2e viruses retained growth characteristics attributable to traditional LAIV viruses and induced robust influenza-specific antibody responses in BALB/c mice, although M2e-specific antibodies were raised only after two-dose vaccination with LAIV+4M2e viruses. Mice immunized with either LAIV or LAIV+4M2e viruses were fully protected against a panel of heterologous influenza challenge viruses suggesting that antibody and cell-mediated immunity contributed to the protection. The protective role of the M2e-specific antibody was seen in passive serum transfer experiments, where enhancement in the survival rates between classical LAIV and chimeric H3N2+4M2e LAIV was demonstrated for H3N2 and H5N1 heterologous challenge viruses. Overall, the results of our study suggest that M2e-specific antibodies induced by recombinant LAIV+4M2e in addition to cellular immunity by LAIV play an important role in conferring protection against heterologous viruses. View Full-Text
Keywords: influenza; universal influenza vaccine; live attenuated influenza vaccine; M2e antigen; recombinant influenza virus; cross-protection; mouse model; B-cell immunity; T-cell immunity; innate immunity influenza; universal influenza vaccine; live attenuated influenza vaccine; M2e antigen; recombinant influenza virus; cross-protection; mouse model; B-cell immunity; T-cell immunity; innate immunity
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MDPI and ACS Style

Kotomina, T.; Isakova-Sivak, I.; Kim, K.-H.; Park, B.R.; Jung, Y.-J.; Lee, Y.; Mezhenskaya, D.; Matyushenko, V.; Kang, S.-M.; Rudenko, L. Generation and Characterization of Universal Live-Attenuated Influenza Vaccine Candidates Containing Multiple M2e Epitopes. Vaccines 2020, 8, 648. https://doi.org/10.3390/vaccines8040648

AMA Style

Kotomina T, Isakova-Sivak I, Kim K-H, Park BR, Jung Y-J, Lee Y, Mezhenskaya D, Matyushenko V, Kang S-M, Rudenko L. Generation and Characterization of Universal Live-Attenuated Influenza Vaccine Candidates Containing Multiple M2e Epitopes. Vaccines. 2020; 8(4):648. https://doi.org/10.3390/vaccines8040648

Chicago/Turabian Style

Kotomina, Tatiana, Irina Isakova-Sivak, Ki-Hye Kim, Bo R. Park, Yu-Jin Jung, Youri Lee, Daria Mezhenskaya, Victoria Matyushenko, Sang-Moo Kang, and Larisa Rudenko. 2020. "Generation and Characterization of Universal Live-Attenuated Influenza Vaccine Candidates Containing Multiple M2e Epitopes" Vaccines 8, no. 4: 648. https://doi.org/10.3390/vaccines8040648

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