Pathogen-Host Interactions: Implications for Vaccine Design

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 October 2018) | Viewed by 35706

Special Issue Editor


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Guest Editor
Department of Microbiology, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Interests: vaccines; mucosal immunity; respiratory viruses; pathogenesis; animal models; biocontainment
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Special Issue Information

Dear Colleagues,

How can studies on host-pathogen interactions influence the development of vaccines? What are the implications of the coevolution of a pathogen with its host for vaccine development? The outcome of the interaction of the host with a pathogen dictates the clinical severity of disease resulting from infection by that pathogen. This same basic principle also applies to the development of vaccines based on live, attenuated versions of a pathogen. Recent advances in cell culture systems, including 3D cultures and organoids, and animal models, are instrumental in gaining insight into pathogenesis and host immune response to infection by a pathogen or immunization. An improved understanding of host-pathogen interactions will drive forward the development of vaccines.

This Special Issue of Vaccines will bring together a collection of reviews and peer-reviewed articles on cutting-edge research that is focused on detailing the implications of host-pathogen interactions or host-vaccine interactions on vaccine design and effectiveness. Importantly, this Special Issue also aims to address the implications of host-pathogen or host-vaccine interactions for the identification of correlates of protection induced by vaccination. Perspectives, review articles, and original research articles are invited from specialists in host-pathogen interactions, host-vaccine interactions, vaccine development, vaccine delivery, identification of immunogens, host immune response, and clinical and/or preclinical trials.

Dr. Randy Albrecht
Guest Editor

Manuscript Submission Information

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Keywords

  • host-pathogen interactions
  • host-pathogen coevolution
  • host-vaccine interactions
  • vaccine development
  • immunogen design
  • immune evasion
  • mucosal immunity

Published Papers (7 papers)

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Research

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15 pages, 5473 KiB  
Article
TIV Vaccination Modulates Host Responses to Influenza Virus Infection that Correlate with Protection against Bacterial Superinfection
by Angela Choi, Ioanna Christopoulou, Xavier Saelens, Adolfo García-Sastre and Michael Schotsaert
Vaccines 2019, 7(3), 113; https://doi.org/10.3390/vaccines7030113 - 12 Sep 2019
Cited by 6 | Viewed by 4175
Abstract
Background: Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the [...] Read more.
Background: Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the effect of suboptimal vaccination on the outcome of post-influenza bacterial superinfection. Methods: We established a mouse vaccination model that allows control of disease severity after influenza virus infection despite inefficient induction of virus-neutralizing antibody titers by vaccination. We investigated the effect of vaccination on virus-induced host immune responses and on the outcome of superinfection with Staphylococcus aureus. Results: Vaccination with trivalent inactivated virus vaccine (TIV) reduced morbidity after influenza A virus infection but did not prevent virus replication completely. Despite the poor induction of influenza-specific antibodies, TIV protected from mortality after bacterial superinfection. Vaccination limited loss of alveolar macrophages and reduced levels of infiltrating pulmonary monocytes after influenza virus infection. Interestingly, TIV vaccination resulted in enhanced levels of eosinophils after influenza virus infection and recruitment of neutrophils in both lungs and mediastinal lymph nodes after bacterial superinfection. Conclusion: These observations highlight the importance of disease modulation by influenza vaccination, even when suboptimal, and suggest that influenza vaccination is still beneficial to protect during bacterial superinfection in the absence of complete virus neutralization. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
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15 pages, 1901 KiB  
Article
Heterotypic Neuraminidase Antibodies Against Different A(H1N1) Strains are Elicited after Seasonal Influenza Vaccination
by Jose Manuel Mendez-Legaza, Raúl Ortiz de Lejarazu and Ivan Sanz
Vaccines 2019, 7(1), 30; https://doi.org/10.3390/vaccines7010030 - 13 Mar 2019
Cited by 9 | Viewed by 3802
Abstract
Neuraminidase (NA) content is not standardized in current seasonal influenza vaccines; neither anti-NA antibodies (anti-NA Abs) are measured nor is it well-defined as a correlate of humoral protection. In this work, the presence of NA1 antibodies against classical A(H1N1) and A(H1N1) pdm09 subtypes [...] Read more.
Neuraminidase (NA) content is not standardized in current seasonal influenza vaccines; neither anti-NA antibodies (anti-NA Abs) are measured nor is it well-defined as a correlate of humoral protection. In this work, the presence of NA1 antibodies against classical A(H1N1) and A(H1N1) pdm09 subtypes was studied before and after vaccination with seasonal vaccines containing A/California/07/2009 strain (A(H1N1) pdm09 subtype). By Enzyme-Linked Lectin Assay (ELLA; Consortium for the Standardization of Influenza Seroepidemiology), we analyzed serum samples from two different cohorts (adults and elderly). The presence of anti-NA Abs at titers ≥1/40 against classical A(H1N1) and A(H1N1) pdm09 subtypes were frequently found in both age groups, in 81.3% and 96.3% of adults and elderly, respectively. The higher titers of anti-NA Abs (NAI titers) were detected more frequently against classical A(H1N1) strains according to the expected age when the first flu infection takes place. In this way, an Original Antigenic Sin phenomenon related to NA seems to be part of the immune response against flu. Seasonal-vaccination induced homologous seroconversion against NA of A(H1N1) pdm09 subtype in 52.5% and 55.0%, and increased the Geometric Mean Titers (GMTs) in 70.0% and 78.8% of adults and elderly, respectively. Seasonal vaccination also induced a heterotypic anti-NA Abs response against classical A(H1N1) strains (seroconversion at least in 8.8% and 11.3% of adults and elderly, respectively, and an increase in GMTs of at least 28.0% in both age groups). These anti-NA Abs responses occur even though the seasonal vaccine does not contain a standardized amount of NA. This work demonstrates that seasonal vaccines containing the A(H1N1) pdm09 subtype induce a broad antibody response against NA1, that may be a target for future influenza vaccines. Our study is one of the first to analyze the presence of Abs against NA and the response mediated by NAI titers after seasonal influenza vaccination. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
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Review

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10 pages, 592 KiB  
Review
Moving from Empirical to Rational Vaccine Design in the ‘Omics’ Era
by Mansi Sharma, Florian Krammer, Adolfo García-Sastre and Shashank Tripathi
Vaccines 2019, 7(3), 89; https://doi.org/10.3390/vaccines7030089 - 14 Aug 2019
Cited by 17 | Viewed by 7696
Abstract
An ideal vaccine provides long lasting protection against a pathogen by eliciting a well-rounded immune response which engages both innate and adaptive immunity. However, we have a limited understanding of how components of innate immunity, antibody and cell-mediated adaptive immunity interact and function [...] Read more.
An ideal vaccine provides long lasting protection against a pathogen by eliciting a well-rounded immune response which engages both innate and adaptive immunity. However, we have a limited understanding of how components of innate immunity, antibody and cell-mediated adaptive immunity interact and function together at a systems level. With advances in high-throughput ‘Omics’ methodologies it has become possible to capture global changes in the host, at a cellular and molecular level, that are induced by vaccination and infection. Analysis of these datasets has shown the promise of discovering mechanisms behind vaccine mediated protection, immunological memory, adverse effects as well as development of more efficient antigens and adjuvants. In this review, we will discuss how systems vaccinology takes advantage of new technology platforms and big data analysis, to enable the rational development of better vaccines. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
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11 pages, 252 KiB  
Review
Role of Type I Interferons on Filovirus Pathogenesis
by Beatriz Escudero-Pérez and César Muñoz-Fontela
Vaccines 2019, 7(1), 22; https://doi.org/10.3390/vaccines7010022 - 20 Feb 2019
Cited by 8 | Viewed by 3664
Abstract
Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the [...] Read more.
Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
13 pages, 293 KiB  
Review
Complementary Role of CD4+ T Cells in Response to Pneumococcal Polysaccharide Vaccines in Humans
by Vibha Jha and Edward N. Janoff
Vaccines 2019, 7(1), 18; https://doi.org/10.3390/vaccines7010018 - 11 Feb 2019
Cited by 18 | Viewed by 4593
Abstract
Bacterial pathogens expressing capsular polysaccharides are common causes of mucosal infections (pneumonia, intestinal), as well as often fatal, invasive infections (meningitis, bloodstream infections) in children and adults worldwide. These chemically simple but structurally complex carbohydrate structures on the bacterial surface confer resistance to [...] Read more.
Bacterial pathogens expressing capsular polysaccharides are common causes of mucosal infections (pneumonia, intestinal), as well as often fatal, invasive infections (meningitis, bloodstream infections) in children and adults worldwide. These chemically simple but structurally complex carbohydrate structures on the bacterial surface confer resistance to recognition and clearance by the immune system through a range of mechanisms. Such recognition of capsular polysaccharides may be reduced by their limited ability to directly stimulate B cells and the T cells that may facilitate these humoral responses. The capsules may promote the evasion of complement deposition and activation and may sterically shield the recognition of other subjacent protein antigens by innate factors. Antibodies to capsular polysaccharides, elicited by infection and vaccines, may overcome these obstacles and facilitate bacterial agglutination at mucosal surfaces, as well as the opsonization and clearance of these organisms in tissues and the systemic compartment. However, the immunogenicity of these antigens may be limited by their lack of direct recognition by T cells (“T-independent” antigens) and their restricted ability to generate effective memory responses. In this review, we consider the mechanisms by which polysaccharides may initiate B cell responses and specific antibody responses and the role of T cells, particularly CD4+ follicular helper (TFH) cells to support this process. In addition, we also consider more recent counterintuitive data that capsular polysaccharides themselves may bind major histocompatibility antigen HLA class II to provide a more physiologic mechanism of T cell enhancement of B cell responses to capsular polysaccharides. Defining the contributions of T cells in the generation of effective humoral responses to the capsular polysaccharides will have important implications for understanding and translating this immunobiology for the development of more effective vaccines, to prevent the morbidity and mortality associated with these common mucosal and invasive pathogens in populations at risk. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
20 pages, 1720 KiB  
Review
Time to Micromanage the Pathogen-Host-Vector Interface: Considerations for Vaccine Development
by Jessica E. Manning and Tineke Cantaert
Vaccines 2019, 7(1), 10; https://doi.org/10.3390/vaccines7010010 - 21 Jan 2019
Cited by 16 | Viewed by 6822
Abstract
The current increase in vector-borne disease worldwide necessitates novel approaches to vaccine development targeted to pathogens delivered by blood-feeding arthropod vectors into the host skin. A concept that is gaining traction in recent years is the contribution of the vector or vector-derived components, [...] Read more.
The current increase in vector-borne disease worldwide necessitates novel approaches to vaccine development targeted to pathogens delivered by blood-feeding arthropod vectors into the host skin. A concept that is gaining traction in recent years is the contribution of the vector or vector-derived components, like salivary proteins, to host-pathogen interactions. Indeed, the triad of vector-host-pathogen interactions in the skin microenvironment can influence host innate and adaptive responses alike, providing an advantage to the pathogen to establish infection. A better understanding of this “bite site” microenvironment, along with how host and vector local microbiomes immunomodulate responses to pathogens, is required for future vaccines for vector-borne diseases. Microneedle administration of such vaccines may more closely mimic vector deposition of pathogen and saliva into the skin with the added benefit of near painless vaccine delivery. Focusing on the ‘micro’–from microenvironments to microbiomes to microneedles–may yield an improved generation of vector-borne disease vaccines in today’s increasingly complex world. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
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Other

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11 pages, 4012 KiB  
Brief Report
Attenuation and Stability of CHIKV-NoLS, a Live-Attenuated Chikungunya Virus Vaccine Candidate
by Eranga Abeyratne, Joseph R. Freitas, Ali Zaid, Suresh Mahalingam and Adam Taylor
Vaccines 2019, 7(1), 2; https://doi.org/10.3390/vaccines7010002 - 22 Dec 2018
Cited by 10 | Viewed by 3851
Abstract
Our previous investigation of the nucleolar localisation sequence (NoLS) of chikungunya virus (CHIKV) capsid protein demonstrated the role of capsid in CHIKV virulence. Mutating the NoLS of capsid in CHIKV led to the development of a unique live-attenuated CHIKV vaccine candidate, termed CHIKV-NoLS. [...] Read more.
Our previous investigation of the nucleolar localisation sequence (NoLS) of chikungunya virus (CHIKV) capsid protein demonstrated the role of capsid in CHIKV virulence. Mutating the NoLS of capsid in CHIKV led to the development of a unique live-attenuated CHIKV vaccine candidate, termed CHIKV-NoLS. CHIKV-NoLS-immunised mice developed long-term immunity from CHIKV infection after a single dose. To further evaluate CHIKV-NoLS attenuation and suitability as a vaccine, we examined the footpad of inoculated mice for underlying CHIKV-NoLS-induced immunopathology by histological and flow cytometric analysis. In comparison to CHIKV-WT-infected mice, CHIKV-NoLS-inoculated mice exhibited minimal inflammation and tissue damage. To examine the stability of attenuation, the plaque phenotype and replication kinetics of CHIKV-NoLS were determined following extended in vitro passage. The average plaque size of CHIKV-NoLS remained notably smaller than CHIKV-WT after extended passage and attenuated replication was maintained. To examine thermostability, CHIKV-NoLS was stored at 21 °C, 4 °C, −20 °C and −80 °C and infectious CHIKV-NoLS quantified up to 84 days. The infectious titre of CHIKV-NoLS remains stable after 56 days when stored at either −20 °C or −80 °C. Interestingly, unlike CHIKV-WT, the infectious titre of CHIKV-NoLS is not sensitive to freeze thaw cycles. These data further demonstrate preclinical safety and stability of CHIKV-NoLS. Full article
(This article belongs to the Special Issue Pathogen-Host Interactions: Implications for Vaccine Design)
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