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Vaccines
Special Issues
Viral Imprinting and Vaccine Design of Influenza and Other Viruses
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Viral Imprinting and Vaccine Design of Influenza and Other Viruses

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

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 34493

Special Issue Editor

Dr. Alyson Kelvin

E-Mail Website
Guest Editor
Department of Pediatrics, Dalhousie University, Halifax, Canada
Interests: Influenza viruses; Imprinting; Vaccine design; Vaccine responses; Emerging viruses

Special Issue Information

Dear Colleagues,

A host’s first encounter with a virus or viral vaccine results in viral or vaccine imprinting. The imprinting event initiates a cascade of immune events that culminates in immunological memory impacting subsequent host responses to viruses with similar homology. Viral imprinting is a major determinant of viral disease outcome and vaccine efficacy for both circulating and emerging viruses. Well known examples of viral imprinting include influenza virus, respiratory syncytial virus, and dengue viral imprinting. The importance of imprinting must be considered in vaccine design because as seen with RSV, Dengue, and influenza vaccines, first exposure imprinting has a direct impact on vaccine efficacy and vaccine complications. Other viruses that should also be considered in the conversation of viral imprinting include viruses with related yet antigenically divergent family members including Ebola viruses (filoviruses family) and other arboviruses including Zika virus, chikungunya virus, and yellow fever virus. This Special Issue of Vaccines highlights the new and emerging field of viral imprinting and its importance in vaccine design and development. This issue includes articles investigating the epidemiological outcomes of viral imprinting and preimmunity in the context of current disease outbreaks as well as mechanistic studies focusing on imprinting and memory recall during secondary exposure. With this collection we aim to provide a foundation for conceptualizing the universality of the viral imprinting responses in the host and how this can be leveraged for vaccine design.

Dr. Alyson Kelvin
Guest Editor

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

  • Imprinting
  • Viral Imprinting
  • Influenza viruses
  • Dengue virus
  • Yellow Fever Virus
  • West Nile Virus
  • Flavivirus
  • Chikungunya Virus
  • Filovirus
  • Respiratory Syncytial Virus
  • Vaccine design
  • Vaccine responses
  • Preimmunity
  • Immune history
  • Broadly neutralizing antibodies
  • Universal vaccine
  • Memory B cells
  • Antibody dependent cell cytotoxicity
  • Antibody enhanced disease Sequential infection
  • Sequential vaccination

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Published Papers (7 papers)

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Research

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15 pages, 3468 KiB  
Article
Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung
by Ermias Jirru, Stefi Lee, Rebecca Harris, Jianjun Yang, Soo Jung Cho and Heather Stout-Delgado
Vaccines 2020, 8(2), 298; https://doi.org/10.3390/vaccines8020298 - 11 Jun 2020
Cited by 4 | Viewed by 2905
Abstract
Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal [...] Read more.
Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 102 PFU). Control and influenza-infected mice were instilled with PBS or S. pneumoniae (1 × 103 CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with S. pneumoniae. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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16 pages, 1050 KiB  
Article
Immune Pressure on Polymorphous Influenza B Populations Results in Diverse Hemagglutinin Escape Mutants and Lineage Switching
by Ewan P. Plant, Hasmik Manukyan, Jose L. Sanchez, Majid Laassri and Zhiping Ye
Vaccines 2020, 8(1), 125; https://doi.org/10.3390/vaccines8010125 - 11 Mar 2020
Cited by 5 | Viewed by 2853
Abstract
Mutations arise in the genomes of progeny viruses during infection. Mutations that occur in epitopes targeted by host antibodies allow the progeny virus to escape the host adaptive, B-cell mediated antibody immune response. Major epitopes have been identified in influenza B virus (IBV) [...] Read more.
Mutations arise in the genomes of progeny viruses during infection. Mutations that occur in epitopes targeted by host antibodies allow the progeny virus to escape the host adaptive, B-cell mediated antibody immune response. Major epitopes have been identified in influenza B virus (IBV) hemagglutinin (HA) protein. However, IBV strains maintain a seasonal presence in the human population and changes in IBV genomes in response to immune pressure are not well characterized. There are two lineages of IBV that have circulated in the human population since the 1980s, B-Victoria and B-Yamagata. It is hypothesized that early exposure to one influenza subtype leads to immunodominance. Subsequent seasonal vaccination or exposure to new subtypes may modify subsequent immune responses, which, in turn, results in selection of escape mutations in the viral genome. Here we show that while some mutations do occur in known epitopes suggesting antibody escape, many mutations occur in other parts of the HA protein. Analysis of mutations outside of the known epitopes revealed that these mutations occurred at the same amino acid position in viruses from each of the two IBV lineages. Interestingly, where the amino acid sequence differed between viruses from each lineage, reciprocal amino acid changes were observed. That is, the virus from the Yamagata lineage become more like the Victoria lineage virus and vice versa. Our results suggest that some IBV HA sequences are constrained to specific amino acid codons when viruses are cultured in the presence of antibodies. Some changes to the known antigenic regions may also be restricted in a lineage-dependent manner. Questions remain regarding the mechanisms underlying these results. The presence of amino acid residues that are constrained within the HA may provide a new target for universal vaccines for IBV. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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26 pages, 1204 KiB  
Article
Mapping Host-Related Correlates of Influenza Vaccine-Induced Immune Response: An Umbrella Review of the Available Systematic Reviews and Meta-Analyses
by Alexander Domnich, Ilaria Manini, Giovanna Elisa Calabrò, Chiara de Waure and Emanuele Montomoli
Vaccines 2019, 7(4), 215; https://doi.org/10.3390/vaccines7040215 - 13 Dec 2019
Cited by 17 | Viewed by 4184
Abstract
Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza [...] Read more.
Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus- and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed—these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette–Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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20 pages, 3959 KiB  
Article
Historical H1N1 Influenza Virus Imprinting Increases Vaccine Protection by Influencing the Activity and Sustained Production of Antibodies Elicited at Vaccination in Ferrets
by Magen E. Francis, Mara McNeil, Nicholas J. Dawe, Mary K. Foley, Morgan L. King, Ted M. Ross and Alyson A. Kelvin
Vaccines 2019, 7(4), 133; https://doi.org/10.3390/vaccines7040133 - 28 Sep 2019
Cited by 22 | Viewed by 5807
Abstract
Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year [...] Read more.
Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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18 pages, 2176 KiB  
Article
An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains
by Weina Sun, Allen Zheng, Robert Miller, Florian Krammer and Peter Palese
Vaccines 2019, 7(3), 117; https://doi.org/10.3390/vaccines7030117 - 18 Sep 2019
Cited by 12 | Viewed by 5317
Abstract
Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel [...] Read more.
Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel inactivated influenza virus vaccine approach that combines these two strategies. We inserted a human consensus M2e epitope into the immunodominant antigenic site (Ca2 site) of three different chimeric HAs (cHAs). Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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Review

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19 pages, 798 KiB  
Review
Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines
by Ekramy E. Sayedahmed, Ahmed Elkashif, Marwa Alhashimi, Suryaprakash Sambhara and Suresh K. Mittal
Vaccines 2020, 8(4), 574; https://doi.org/10.3390/vaccines8040574 - 1 Oct 2020
Cited by 52 | Viewed by 8033
Abstract
Ever since the discovery of vaccines, many deadly diseases have been contained worldwide, ultimately culminating in the eradication of smallpox and polio, which represented significant medical achievements in human health. However, this does not account for the threat influenza poses on public health. [...] Read more.
Ever since the discovery of vaccines, many deadly diseases have been contained worldwide, ultimately culminating in the eradication of smallpox and polio, which represented significant medical achievements in human health. However, this does not account for the threat influenza poses on public health. The currently licensed seasonal influenza vaccines primarily confer excellent strain-specific protection. In addition to the seasonal influenza viruses, the emergence and spread of avian influenza pandemic viruses such as H5N1, H7N9, H7N7, and H9N2 to humans have highlighted the urgent need to adopt a new global preparedness for an influenza pandemic. It is vital to explore new strategies for the development of effective vaccines for pandemic and seasonal influenza viruses. The new vaccine approaches should provide durable and broad protection with the capability of large-scale vaccine production within a short time. The adenoviral (Ad) vector-based vaccine platform offers a robust egg-independent production system for manufacturing large numbers of influenza vaccines inexpensively in a short timeframe. In this review, we discuss the progress in the development of Ad vector-based influenza vaccines and their potential in designing a universal influenza vaccine. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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18 pages, 321 KiB  
Review
Immune Imprinting in the Influenza Ferret Model
by Amanda L. Skarlupka and Ted M. Ross
Vaccines 2020, 8(2), 173; https://doi.org/10.3390/vaccines8020173 - 8 Apr 2020
Cited by 12 | Viewed by 3388
Abstract
The initial exposure to influenza virus usually occurs during childhood. This imprinting has long-lasting effects on the immune responses to subsequent infections and vaccinations. Animal models that are used to investigate influenza pathogenesis and vaccination do recapitulate the pre-immune history in the human [...] Read more.
The initial exposure to influenza virus usually occurs during childhood. This imprinting has long-lasting effects on the immune responses to subsequent infections and vaccinations. Animal models that are used to investigate influenza pathogenesis and vaccination do recapitulate the pre-immune history in the human population. The establishment of influenza pre-immune ferret models is necessary for understanding infection and transmission and for designing efficacious vaccines. Full article
(This article belongs to the Special Issue Viral Imprinting and Vaccine Design of Influenza and Other Viruses)
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