scholarly journals New Technologies for Influenza Vaccines

2020 ◽  
Vol 8 (11) ◽  
pp. 1745
Author(s):  
Steven Rockman ◽  
Karen L. Laurie ◽  
Simone Parkes ◽  
Adam Wheatley ◽  
Ian G. Barr
Keyword(s):  
Computational Biology ◽  
Influenza Vaccine ◽  
New Technologies ◽  
Vaccine Development ◽  
Influenza Vaccines ◽  
Lead Times ◽  
Next Generation ◽  
Development Cycle ◽  
Universal Influenza Vaccine

Vaccine development has been hampered by the long lead times and the high cost required to reach the market. The 2020 pandemic, caused by a new coronavirus (SARS-CoV-2) that was first reported in late 2019, has seen unprecedented rapid activity to generate a vaccine, which belies the traditional vaccine development cycle. Critically, much of this progress has been leveraged off existing technologies, many of which had their beginnings in influenza vaccine development. This commentary outlines the most promising of the next generation of non-egg-based influenza vaccines including new manufacturing platforms, structure-based antigen design/computational biology, protein-based vaccines including recombinant technologies, nanoparticles, gene- and vector-based technologies, as well as an update on activities around a universal influenza vaccine.

scholarly journals Designed Nanoparticles Elicit Cross-Reactive Antibody Responses To Conserved Influenza Virus Hemagglutinin Stem Epitopes

2019 ◽  
Author(s):  
Dustin M. McCraw ◽  
Mallory L. Myers ◽  
Neetu M. Gulati ◽  
John R. Gallagher ◽  
Alexander J. Kim ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Vaccine Development ◽  
Cross Reactivity ◽  
Surface Glycoprotein ◽  
Influenza Vaccines ◽  
Health Concern ◽  
Public Health Issue ◽  
Lethal Challenge ◽  
Universal Influenza Vaccine

AbstractDespite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that an alpha-helical fragment (helix-A) from the conserved stem region can be displayed on nanoparticles. The stem region of HA on these nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, H1-nanoparticles protected mice from lethal challenge with H1N1 influenza virus. Importantly, antibodies elicited by these nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity. The helix-A stem nanoparticle design represents a novel approach to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens up opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.SignificanceInfluenza virus is a public health issue that affects millions of people globally each year. Commercial influenza vaccines are based on the hemagglutinin (HA) surface glycoprotein, which can change antigenically every year, demanding the manufacture of newly matched vaccines annually. HA stem epitopes have a higher degree of conservation than HA molecules contained in conventional vaccine formulations and we demonstrate that we are able to design nanoparticles that display hundreds of HA stem fragments on nanoparticles. These designed nanoparticles are heat-stable, elicit antibodies to the HA stem, confer protection in mouse challenge models, and show cross-reactivity between HA subtypes. This technology provides promising opportunities to improve seasonal vaccines, develop pandemic preparedness vaccines, and facilitate the development of a universal influenza vaccine.

scholarly journals Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

2021 ◽  
Author(s):  
Mengling Li ◽  
Pengju Guo ◽  
Cen Chen ◽  
Helong Feng ◽  
Wanpo Zhang ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Matrix Protein ◽  
Vaccine Development ◽  
Influenza Pandemic ◽  
Bacteriophage T4 ◽  
Influenza Vaccines ◽  
Next Generation ◽  
Vaccine Platform ◽  
Virus Challenge ◽  
Virus Like Particle

Developing influenza vaccines that protect against a broad range of viruses is a public health priority, and several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is immunogenic, and vaccine platforms that can incorporate multiple antigens with enhanced immunogenicity are desperately needed. In this study, we provided proof-of-concept for the development of next-generation influenza vaccine using T4 phage virus-like particle (VLP) platform. With extracellular domain of influenza matrix protein 2 (M2e) as a readout, we showed that more than 1,280 M2e molecules can be assembled on a 120×90 nanometer phage capsid to form T4-M2e VLPs, which are highly immunogenic and induced complete protection against influenza virus challenge without any addition adjuvant. Potentially, additional conserved antigens or molecular adjuvants could be incorporated into the T4-M2e VLPs to customize influenza vaccines to address different issues. All the components of T4 VLP vaccines can be mass-produced in E. coli in a short time, therefore, providing a rapid approach to deal with the potential influenza pandemic.

scholarly journals Prospects and Challenges in the Development of Universal Influenza Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 361 ◽  
Author(s):  
Anders Madsen ◽  
Rebecca Jane Cox
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Vaccine Design ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Next Generation ◽  
Universal Influenza Vaccine

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.

scholarly journals M2e-Based Influenza Vaccines with Nucleoprotein: A Review

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 739
Author(s):  
Mei Peng Tan ◽  
Wen Siang Tan ◽  
Noorjahan Banu Mohamed Alitheen ◽  
Wei Boon Yap
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Matrix Protein ◽  
Severe Disease ◽  
Chimeric Protein ◽  
Influenza Vaccines ◽  
Cell Responses ◽  
Hospitalization Rates ◽  
Humoral Responses ◽  
Universal Influenza Vaccine

Discovery of conserved antigens for universal influenza vaccines warrants solutions to a number of concerns pertinent to the currently licensed influenza vaccines, such as annual reformulation and mismatching with the circulating subtypes. The latter causes low vaccine efficacies, and hence leads to severe disease complications and high hospitalization rates among susceptible and immunocompromised individuals. A universal influenza vaccine ensures cross-protection against all influenza subtypes due to the presence of conserved epitopes that are found in the majority of, if not all, influenza types and subtypes, e.g., influenza matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Despite its relatively low immunogenicity, influenza M2e has been proven to induce humoral responses in human recipients. Influenza NP, on the other hand, promotes remarkable anti-influenza T-cell responses. Additionally, NP subunits are able to assemble into particles which can be further exploited as an adjuvant carrier for M2e peptide. Practically, the T-cell immunodominance of NP can be transferred to M2e when it is fused and expressed as a chimeric protein in heterologous hosts such as Escherichia coli without compromising the antigenicity. Given the ability of NP-M2e fusion protein in inducing cross-protective anti-influenza cell-mediated and humoral immunity, its potential as a universal influenza vaccine is therefore worth further exploration.

Design, synthesis and primary immunologic evaluation of M2e-CRM197 conjugate as a universal influenza vaccine candidate

2020 ◽  
Vol 21 ◽  
Author(s):  
Lu Xu ◽  
Chun Zhang ◽  
Jing Zhang ◽  
Rong Yu ◽  
Zhiguo Su
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza A Virus ◽  
Influenza A ◽  
Vaccine Development ◽  
Acute Infection ◽  
Acid Hydrazide ◽  
Influenza Viruses ◽  
Carrier Protein ◽  
Universal Influenza Vaccine

Background: Influenza is a contagious respiratory illness caused by acute infection of influenza viruses, among which influenza A virus causes epidemic seasonal infection nearly every year. Along with unpredictability of evolving influenza A virus and time-consuming vaccine development cycles, novel universal influenza vaccine designed to induce broadly cross-reactive immune responses against frequently mutant influenza A virus strains are greatly urgent. Objective: The aim of this study was to synthesize a novel vaccine through the dual-site specific conjugation of the constant epitope of 23 amino acids (M2e) of influenza A virus with highly immunogenic carrier protein of cross-reacting material (CRM197) under denaturation, and evaluate its primary immunogenicity in mice. Methods: The antigen (M2e) and the carrier protein (CRM197) were linked with different type of hetero-functionalized linkers, α-maleimide-ε-hydrazide polyethylene glycol 2k (MAL-PEG-HZ) and N-β-maleimidopropionic acid hydrazide (BMPH) separately. The immunogenicity of the M2e-CRM197 conjugates with different type of linkers was evaluated in mice, and the M2e-specific total IgG and IgG-isotypes were determined by ELSIA. Results: Immunogenicity study revealed that anti-M2e antibody could be induced by the conjugate products, M2e-PEGCRM197 and M2e-BMPH-CRM197, were approximately 30 and 90-fold higher than that of M2e group. In addition, the antiM2e antibody level induced by M2e-PEG-CRM197 conjugate was three times higher than that of M2e-BMPH-CRM197 conjugate, and the former could simultaneously activate both cellar and humoral immune responses. Conclusions: The M2e-CRM197 conjugated vaccines we synthesized in this study are highly immunogenic compared with M2e alone. Besides, evidences were presented here indicated that the hydrophilic, non-immunogenic and biocompatible chain of the cross-linker might be a better choice for development of conjugate vaccine.

Tracking progress in universal influenza vaccine development

2020 ◽  
Vol 40 ◽  
pp. 28-36 ◽  
Author(s):  
Julie Ostrowsky ◽  
Meredith Arpey ◽  
Kristine Moore ◽  
Michael Osterholm ◽  
Martin Friede ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Development ◽  
Universal Influenza Vaccine

Conventional influenza vaccines influence the performance of a universal influenza vaccine in mice

Vaccine ◽  
2018 ◽  
Vol 36 (7) ◽  
pp. 1008-1015 ◽  
Author(s):  
Janelle Rowell ◽  
Chia-Yun Lo ◽  
Graeme E. Price ◽  
Julia A. Misplon ◽  
Suzanne L. Epstein ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccines ◽  
Universal Influenza Vaccine

scholarly journals Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 169 ◽  
Author(s):  
Jazayeri ◽  
Poh
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Neutralizing Antibodies ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Influenza Vaccines ◽  
Influenza Pandemics ◽  
Host Immune Responses ◽  
Production Platform ◽  
Universal Influenza Vaccine

Vaccination is still the most efficient way to prevent an infection with influenza viruses. Nevertheless, existing commercial vaccines face serious limitations such as availability during epidemic outbreaks and their efficacy. Existing seasonal influenza vaccines mostly induce antibody responses to the surface proteins of influenza viruses, which frequently change due to antigenic shift and or drift, thus allowing influenza viruses to avoid neutralizing antibodies. Hence, influenza vaccines need a yearly formulation to protect against new seasonal viruses. A broadly protective or universal influenza vaccine must induce effective humoral as well as cellular immunity against conserved influenza antigens, offer good protection against influenza pandemics, be safe, and have a fast production platform. Nanotechnology has great potential to improve vaccine delivery, immunogenicity, and host immune responses. As new strains of human epidemic influenza virus strains could originate from poultry and swine viruses, development of a new universal influenza vaccine will require the immune responses to be directed against viruses from different hosts. This review discusses how the new vaccine platforms and nanoparticles can be beneficial in the development of a broadly protective, universal influenza vaccine.

scholarly journals Influenza vaccines: the potential benefits of cell-culture isolation and manufacturing

2020 ◽  
Vol 8 ◽  
pp. 251513552090812
Author(s):  
Sankarasubramanian Rajaram ◽  
Constantina Boikos ◽  
Daniele K. Gelone ◽  
Ashesh Gandhi
Keyword(s):  
Cell Culture ◽  
Influenza Vaccine ◽  
Vaccine Development ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Influenza Vaccines ◽  
World Health ◽  
Severe Illness ◽  
Vaccine Production ◽  
Culture Technology

Influenza continues to cause severe illness in millions and deaths in hundreds of thousands annually. Vaccines are used to prevent influenza outbreaks, however, the influenza virus mutates and annual vaccination is required for optimal protection. Vaccine effectiveness is also affected by other potential factors such as the human immune system, a mismatch with the chosen candidate virus, and egg adaptation associated with egg-based vaccine production. This article reviews the influenza vaccine development process and describes the implications of the changes to the cell-culture process and vaccine strain recommendations by the World Health Organization since the 2017 season. The traditional manufacturing process for influenza vaccines relies on fertilized chicken eggs that are used for vaccine production. Vaccines must be produced in large volumes and the complete process requires approximately 6 months for the egg-based process. In addition, egg adaptation of seed viruses occurs when viruses adapt to avian receptors found within eggs to allow for growth in eggs. These changes to key viral antigens may result in antigenic mismatch and thereby reduce vaccine effectiveness. By contrast, cell-derived seed viruses do not require fertilized eggs and eliminate the potential for egg-adapted changes. As a result, cell-culture technology improves the match between the vaccine virus strain and the vaccine selected strain, and has been associated with increased vaccine effectiveness during a predominantly H3N2 season. During the 2017–2018 influenza season, a small number of studies conducted in the United States compared the effectiveness of egg-based and cell-culture vaccines and are described here. These observational and retrospective studies demonstrate that inactivated cell-culture vaccines were more effective than egg-based vaccines. Adoption of cell-culture technology for influenza vaccine manufacturing has been reported to improve manufacturing efficiency and the additional benefit of improving vaccine effectiveness is a key factor for future policy making considerations.

scholarly journals Targeting Antigens for Universal Influenza Vaccine Development

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 973
Author(s):  
Quyen-Thi Nguyen ◽  
Young-Ki Choi
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Influenza Viruses ◽  
Target Antigen ◽  
Cell Responses ◽  
Universal Influenza Vaccine ◽  
Virus Strains

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.

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