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Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and...
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Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Influenza Virus Vaccines".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 23227

Special Issue Editors

Dr. Ruben Donis

E-Mail Website
Guest Editor
United States Department of Health and Human Services, Washington, DC 20201, USA
Interests: Influenza; emerging infectious diseases; preclinical and clinical development of vaccines; pandemic response
Dr. Leah Watson

E-Mail Website
Co-Guest Editor
United States Department, Health and Human Services, Washington, DC 20201, USA
Interests: influenza; emerging infectious diseases; preclinical and clinical development of vaccines; pandemic response

Special Issue Information

Dear Colleagues,

The unfolding COVID-19 pandemic has shown that the United States and the world do not have the needed infrastructure and capabilities to effectively mitigate emerging influenza pandemics through vaccination. Technology and infrastructure gaps include: (1) rapid vaccine production technologies that support a dramatic reduction in vaccine development time (time to first dose) and can be scaled for massive manufacture, providing vaccine for the entire target population within 4–6 months. (2) In addition, single-dose vaccination regimens, easy administration, and increased efficacy are needed product profile attributes in order to support commercial viability as a means to achieve sustainability.

This Special Issue seeks original contributions on technologies that support the development and licensure of new influenza vaccines that outperform currently licensed vaccines in efficacy, speed, flexibility, and ease of administration. Manuscripts that describe new vaccines that rely on flexible “platform technologies” (e.g., nucleic acid, recombinant proteins, and viral vectors) that shorten the time to develop a pandemic vaccine (from sequence to large-scale manufacture) are of particular interest, especially if they provide increased efficacy and ease of administration relative to current vaccines. Special consideration will be given to manuscripts on technologies to immunize naive populations with a single-dose regimen. Manuscripts that report original research findings on technologies that have demonstrated preclinical efficacy will be prioritized.

This Issue will bring together innovative vaccine technologies for different respiratory viruses that could be integrated and leveraged to develop disruptive vaccines for influenza and other respiratory pathogens with pandemic potential.

Dr. Ruben Donis
Dr. Leah Watson
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • influenza vaccines
  • platform technology
  • rapid vaccine development
  • improved target product profile
  • efficacy

Published Papers (7 papers)

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Research

Jump to: Review, Other

16 pages, 1614 KiB  
Article
Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity
by Min Z. Levine, Crystal Holiday, Yaohui Bai, Weimin Zhong, Feng Liu, Stacie Jefferson, F. Liaini Gross, Wen-pin Tzeng, Louis Fries, Gale Smith, Philippe Boutet, Damien Friel, Bruce L. Innis, Corey P. Mallett, C. Todd Davis, David E. Wentworth, Ian A. York, James Stevens, Jacqueline M. Katz and Terrence Tumpey
Vaccines 2022, 10(11), 1856; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10111856 - 01 Nov 2022
Cited by 2 | Viewed by 1455
Abstract
Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses [...] Read more.
Influenza A(H7N9) viruses remain as a high pandemic threat. The continued evolution of the A(H7N9) viruses poses major challenges in pandemic preparedness strategies through vaccination. We assessed the breadth of the heterologous neutralizing antibody responses against the 3rd and 5th wave A(H7N9) viruses using the 1st wave vaccine sera from 4 vaccine groups: 1. inactivated vaccine with 2.8 μg hemagglutinin (HA)/dose + AS03A; 2. inactivated vaccine with 5.75 μg HA/dose + AS03A; 3. inactivated vaccine with 11.5 μg HA/dose + MF59; and 4. recombinant virus like particle (VLP) vaccine with 15 μg HA/dose + ISCOMATRIX™. Vaccine group 1 had the highest antibody responses to the vaccine virus and the 3rd/5th wave drifted viruses. Notably, the relative levels of cross-reactivity to the drifted viruses as measured by the antibody GMT ratios to the 5th wave viruses were similar across all 4 vaccine groups. The 1st wave vaccines induced robust responses to the 3rd and Pearl River Delta lineage 5th wave viruses but lower cross-reactivity to the highly pathogenic 5th wave A(H7N9) virus. The population in the United States was largely immunologically naive to the A(H7N9) HA. Seasonal vaccination induced cross-reactive neuraminidase inhibition and binding antibodies to N9, but minimal cross-reactive antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies to A(H7N9). Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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17 pages, 2701 KiB  
Article
Development of an ELISA-Based Potency Assay for Inactivated Influenza Vaccines Using Cross-Reactive Nanobodies
by Chung Y. Cheung, Sitara Dubey, Martina Hadrovic, Christina R. Ball, Walter Ramage, Jacqueline U. McDonald, Ruth Harvey, Simon E. Hufton and Othmar G. Engelhardt
Vaccines 2022, 10(9), 1473; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10091473 - 05 Sep 2022
Cited by 4 | Viewed by 1797
Abstract
Inactivated vaccines are the main influenza vaccines used today; these are usually presented as split (detergent-disrupted) or subunit vaccines, while whole-virus-inactivated influenza vaccines are rare. The single radial immune diffusion (SRD) assay has been used as the gold standard potency assay for inactivated [...] Read more.
Inactivated vaccines are the main influenza vaccines used today; these are usually presented as split (detergent-disrupted) or subunit vaccines, while whole-virus-inactivated influenza vaccines are rare. The single radial immune diffusion (SRD) assay has been used as the gold standard potency assay for inactivated influenza vaccines for decades; however, more recently, various alternative potency assays have been proposed. A new potency test should be able to measure the amount of functional antigen in the vaccine, which in the case of influenza vaccines is the haemagglutinin (HA) protein. Potency tests should also be able to detect the loss of potency caused by changes to the structural and functional integrity of HA. To detect such changes, most alternative potency tests proposed to date use antibodies that react with native HA. Due to the frequent changes in influenza vaccine composition, antibodies may need to be updated in line with changes in vaccine viruses. We have developed two ELISA-based potency assays for group 1 influenza A viruses using cross-reactive nanobodies. The nanobodies detect influenza viruses of subtype H1N1 spanning more than three decades, as well as H5N1 viruses, in ELISA. We found that the new ELISA potency assays are sensitive to the nature of the reference antigen (standard) used to quantify vaccine antigens; using standards matched in their presentation to the vaccine type improved correspondence between the ELISA and SRD assays. Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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19 pages, 4526 KiB  
Article
The Highly Productive Thermothelomyces heterothallica C1 Expression System as a Host for Rapid Development of Influenza Vaccines
by Gabor Keresztes, Mark Baer, Mark R. Alfenito, Theo C. Verwoerd, Andriy Kovalchuk, Marilyn G. Wiebe, Tor Kristian Andersen, Markku Saloheimo, Ronen Tchelet, Richard Kensinger, Gunnveig Grødeland and Mark Emalfarb
Vaccines 2022, 10(2), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10020148 - 20 Jan 2022
Cited by 4 | Viewed by 3178
Abstract
(1) Influenza viruses constantly change and evade prior immune responses, forcing seasonal re-vaccinations with updated vaccines. Current FDA-approved vaccine manufacturing technologies are too slow and/or expensive to quickly adapt to mid-season changes in the virus or to the emergence of pandemic strains. Therefore, [...] Read more.
(1) Influenza viruses constantly change and evade prior immune responses, forcing seasonal re-vaccinations with updated vaccines. Current FDA-approved vaccine manufacturing technologies are too slow and/or expensive to quickly adapt to mid-season changes in the virus or to the emergence of pandemic strains. Therefore, cost-effective vaccine technologies that can quickly adapt to newly emerged strains are desirable. (2) The filamentous fungal host Thermothelomyces heterothallica C1 (C1, formerly Myceliophthora thermophila) offers a highly efficient and cost-effective alternative to reliably produce immunogens of vaccine quality at large scale. (3) We showed the utility of the C1 system expressing hemagglutinin (HA) and a HA fusion protein from different H1N1 influenza A virus strains. Mice vaccinated with the C1-derived HA proteins elicited anti-HA immune responses similar, or stronger than mice vaccinated with HA products derived from prototypical expression systems. A challenge study demonstrated that vaccinated mice were protected against the aggressive homologous viral challenge. (4) The C1 expression system is proposed as part of a set of protein expression systems for plug-and-play vaccine manufacturing platforms. Upon the emergence of pathogens of concern these platforms could serve as a quick solution for producing enough vaccines for immunizing the world population in a much shorter time and more affordably than is possible with current platforms. Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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15 pages, 1404 KiB  
Article
Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults
by Joseph Eiden, Gilad Gordon, Carlos Fierro, Renee Herber, Roger Aitchison, Robert Belshe, Harry Greenberg, Daniel Hoft, Yasuko Hatta, Michael J. Moser, Magdalena Tary-Lehmann, Yoshihiro Kawaoka, Gabriele Neumann, Paul Radspinner and Pamuk Bilsel
Vaccines 2021, 9(12), 1388; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9121388 - 24 Nov 2021
Cited by 7 | Viewed by 2293
Abstract
M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single [...] Read more.
M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (106, 107 or 108 tissue culture infectious dose (TCID50)) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo subjects. No subject had fever or a severe reaction to the vaccine. Influenza-specific serum and mucosal antibody responses and B- and T-cell responses were significantly more frequent among vaccinated subjects vs. placebo recipients. The M2SR vaccine was safe and well tolerated and generated dose-dependent durable serum antibody responses against diverse H3N2 influenza strains. M2SR demonstrated a multi-faceted immune response in seronegative and seropositive subjects. Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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Review

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13 pages, 1366 KiB  
Review
Drop the Needle; A Temperature Stable Oral Tablet Vaccine Is Protective against Respiratory Viral Pathogens
by Becca A. Flitter, Molly R. Braun and Sean N. Tucker
Vaccines 2022, 10(4), 593; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10040593 - 12 Apr 2022
Cited by 6 | Viewed by 5723
Abstract
To effectively combat emerging infections and prevent future pandemics, next generation vaccines must be developed quickly, manufactured rapidly, and most critically, administered easily. Next generation vaccines need innovative approaches that prevent infection, severe disease, and reduce community transmission of respiratory pathogens such as [...] Read more.
To effectively combat emerging infections and prevent future pandemics, next generation vaccines must be developed quickly, manufactured rapidly, and most critically, administered easily. Next generation vaccines need innovative approaches that prevent infection, severe disease, and reduce community transmission of respiratory pathogens such as influenza and SARS-CoV-2. Here we review an oral vaccine tablet that can be manufactured and released in less than 16 weeks of antigen design and deployed without the need for cold chain. The oral Ad5 modular vaccine platform utilizes a non-replicating adenoviral vector (rAd5) containing a novel molecular TLR3 adjuvant that is delivered by tablet, not by needle. This enterically coated, room temperature-stable vaccine tablet elicits robust antigen-specific IgA in the gastrointestinal and respiratory tracts and upregulates mucosal homing adhesion molecules on circulating B and T cells. Several influenza antigens have been tested using this novel vaccine approach and demonstrated efficacy in both preclinical animal models and in phase I/II clinical trials, including in a human challenge study. This oral rAd5 vaccine platform technology offers a promising new avenue for aiding in rapid pandemic preparedness and equitable worldwide vaccine distribution. Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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12 pages, 783 KiB  
Review
Innovations in the Insect Cell Expression System for Industrial Recombinant Vaccine Antigen Production
by Manon M. J. Cox
Vaccines 2021, 9(12), 1504; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9121504 - 20 Dec 2021
Cited by 13 | Viewed by 5937
Abstract
The insect cell expression system has previously been proposed as the preferred biosecurity strategy for production of any vaccine, particularly for future influenza pandemic vaccines. The development and regulatory risk for new vaccine candidates is shortened as the platform is already in use [...] Read more.
The insect cell expression system has previously been proposed as the preferred biosecurity strategy for production of any vaccine, particularly for future influenza pandemic vaccines. The development and regulatory risk for new vaccine candidates is shortened as the platform is already in use for the manufacturing of the FDA-licensed seasonal recombinant influenza vaccine Flublok®. Large-scale production capacity is in place and could be used to produce other antigens as well. However, as demonstrated by the 2019 SARS-CoV-2 pandemic the insect cell expression system has limitations that need to be addressed to ensure that recombinant antigens will indeed play a role in combating future pandemics. The greatest challenge may be the ability to produce an adequate quantity of purified antigen in an accelerated manner. This review summarizes recent innovations in technology areas important for enhancing recombinant-protein production levels and shortening development timelines. Opportunities for increasing product concentrations through vector development, cell line engineering, or bioprocessing and for shortening timelines through standardization of manufacturing processes will be presented. Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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Other

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21 pages, 303 KiB  
Perspective
Vaccine Preparedness for the Next Influenza Pandemic: A Regulatory Perspective
by Norman W. Baylor and Jesse L. Goodman
Vaccines 2022, 10(12), 2136; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10122136 - 13 Dec 2022
Viewed by 1436
Abstract
The response to SARS-CoV-2 demonstrated the tremendous potential of investments in vaccine research and development to impact a global pandemic, resulting in the rapid development and deployment of lifesaving vaccines. However, this unprecedented speed was insufficient to either effectively combat initial waves of [...] Read more.
The response to SARS-CoV-2 demonstrated the tremendous potential of investments in vaccine research and development to impact a global pandemic, resulting in the rapid development and deployment of lifesaving vaccines. However, this unprecedented speed was insufficient to either effectively combat initial waves of the pandemic or adapt in real time to new variants. This review focuses on opportunities from a public health oriented regulatory perspective for enhancing research, development, evaluation, production, and monitoring of safety and effectiveness to facilitate more rapid availability of pandemic influenza vaccines. We briefly review regulatory pathways and processes relevant to pandemic influenza, including how they can be strengthened and globally coordinated. We then focus on what we believe are critical opportunities to provide better approaches, tools, and methods to accelerate and improve vaccine development and evaluation and thus greatly enhance pandemic preparedness. In particular, for the improved vaccines needed to respond to a future influenza pandemic better and more rapidly, moving as much of the development and evaluation process as possible into the pre-pandemic period is critical, including through approval and use of analogous seasonal influenza vaccines with defined immune correlates of protection. Full article
(This article belongs to the Special Issue Technologies for Influenza Vaccines that Provide Increased Speed, Efficacy and Ease of Administration)
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