Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus

Kim, Ki-Hye; Lee, Young-Tae; Park, Soo‐Jin; Jung, Yu‐Jin; Lee, Youri; Ko, Eunju; Kim, Yujin; Li, Xuguang; Kang, Sang-Moo

doi:10.1016/j.virol.2019.07.008

Cited by 48 publications

(47 citation statements)

References 56 publications

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“…To determine cell-mediated immune responses, bronchoalveolar lavage (BAL) fluids and lung tissues were collected at day 5 post infection. BAL cells were harvested by infusing 1 mL of PBS into the trachea using a catheter (Exelint International Co., Los Angeles, CA, USA) as described in [ 28 ]. The lung tissues were homogenized and spun on 44%/67% Percoll gradients at 2800 rpm for 15 min.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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“…This is mostly due to the amount and stability of the NA in the vaccines. Enhanced NA–antibody responses can be achieved by delivering NA as a supplement to current IIVs or vaccinating with recombinant or viral vector NA in addition to the seasonal IIVs [ 70 , 71 , 72 , 73 , 74 ].…”

Section: Universal Vaccine Strategiesmentioning

confidence: 99%

Prospects and Challenges in the Development of Universal Influenza Vaccines

Madsen

2020

Vaccines

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Current influenza vaccines offer suboptimal protection and depend on annual reformulation and yearly administration. Vaccine technology has rapidly advanced during the last decade, facilitating development of next-generation influenza vaccines that can target a broader range of influenza viruses. The development and licensure of a universal influenza vaccine could provide a game changing option for the control of influenza by protecting against all influenza A and B viruses. Here we review important findings and considerations regarding the development of universal influenza vaccines and what we can learn from this moving forward with a SARS-CoV-2 vaccine design.

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“…Immunization with 1931 swine H1N1-protected chickens against lethal viral challenge with influenza A/H7N1 virus [ 81 ]. Mice immunized with H1N1 NA DNA vaccines or virus-like particles (VLPs) containing NA from 2009 pH1N1 were protected from lethal influenza A/H5N1 virus challenge [ 82 , 83 , 84 ], and ferrets immunized with inactivated H1N1, purified N1 or N1-based VLPs were partially protected against lethal H5N1 influenza challenge [ 85 , 86 ]. Pigs infected with H1N1 demonstrated high titers of cross-reactive anti-NA antibodies and had decreased symptoms and shedding after subsequent H5N1 challenge [ 87 ].…”

Section: In Vitro and Animal Studiesmentioning

confidence: 99%

Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine

et al. 2020

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Neuraminidase (NA) is an influenza surface protein that helps to free viruses from mucin-associated decoy receptors and to facilitate budding from infected cells. Experiments have demonstrated that anti-NA antibodies protect animals against lethal influenza challenge by numerous strains, while decreasing pulmonary viral titers, symptoms, and lung lesions. Studies in humans during the influenza A/H3N2 pandemic and in healthy volunteers challenged with influenza A/H1N1 showed that anti-NA immunity reduced symptoms, nasopharyngeal viral shedding, and infection rates. Despite the benefits of anti-NA immunity, current vaccines focus on immunity against hemagglutinin and are not standardized to NA content leading to limited and variable NA immunogenicity. Purified NA has been shown to be safe and immunogenic in humans. Supplementing current vaccines with NA may be a simple strategy to improve suboptimal effectiveness. Immunity against NA is likely to be an important component of future universal influenza vaccines.

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Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus

Cited by 48 publications

References 56 publications

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

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

Prospects and Challenges in the Development of Universal Influenza Vaccines

Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine

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