Viral Vector-Based Vaccines and Therapeutics

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Attenuated/Inactivated/Live and Vectored Vaccines".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 6872

Special Issue Editor


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Guest Editor
Department of Pharmacology Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29209, USA
Interests: vector vaccines

Special Issue Information

Dear Colleagues,

Viral vector technology is at the forefront of medical science, revolutionizing approaches to preventing and treating acute and chronic diseases. Engineered to deliver specific genetic material to cells, these vectors provide a robust platform for vaccine development and gene therapy. This innovative method promises to address unmet medical needs and significantly enhances our ability to respond swiftly to emerging health threats. As we deepen our understanding and improve the design of viral vectors, we set the stage for more precise and effective treatments, potentially transforming the global healthcare landscape.

This Special Issue invites contributions that explore the forefront of viral vector research in both vaccine and therapeutic applications. We seek original research, comprehensive reviews, case studies and perspective pieces that examine the design, development and deployment of viral vector-based solutions. The topics of interest include technological innovations, clinical trial results, safety and efficacy analyses, comparative studies and their impact on global health. We also welcome submissions on developing viral vectors for therapeutic purposes, addressing their potential in treating various diseases. Contributions should consider regulatory, ethical and public perception aspects to foster a multidisciplinary dialogue. This platform allows scholars and clinicians to share insights and propel advancements in viral vector-based vaccines and therapeutics. Join us in shaping the future of research and public health in this dynamic field.

Dr. Sujit Pujhari
Guest Editor

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Keywords

  • viral vectors
  • vaccine technology
  • gene therapy
  • immunization strategies
  • vector design
  • vaccine safety
  • vector-based therapeutics

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Published Papers (5 papers)

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Research

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11 pages, 632 KiB  
Article
Intranasal Sendai Virus Vaccination of Seropositive Children 1 to 2 Years of Age in a Phase I Clinical Trial Boosts Immune Responses Toward Human Parainfluenza Virus Type 1
by Elisabeth Adderson, Kim J. Allison, Kristen Branum, Robert E. Sealy, Bart G. Jones, Sherri L. Surman, Rhiannon R. Penkert, Randall T. Hayden, Charles J. Russell, Allen Portner, Karen S. Slobod and Julia L. Hurwitz
Vaccines 2025, 13(4), 430; https://doi.org/10.3390/vaccines13040430 - 19 Apr 2025
Viewed by 216
Abstract
Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower [...] Read more.
Background/Objectives: Human parainfluenza virus type 1 (hPIV-1) is a major cause of serious respiratory diseases in young children. Annually, hPIV-1 results in approximately 10,000 hospitalizations in the United States due to croup, bronchiolitis, and/or pneumonia, and 10,000 deaths worldwide due to acute lower respiratory tract infections among children less than 5 years of age. Despite the burden of disease, no vaccine for hPIV-1 is currently approved. Sendai virus (SeV) is a murine PIV-1. It has structural similarities with hPIV-1 and is currently under clinical development as an hPIV-1 Jennerian vaccine. Attributes of SeV include the following: (a) needleless delivery, (b) rapid and durable serum antibody responses after a single intranasal administration, (c) durable IgG and IgA responses in the nasal mucosa, and (d) use as a platform for recombinant vaccines against multiple pediatric pathogens. Evaluation of the tolerability, safety, and immunogenicity of intranasal SeV in healthy adults and seropositive children 3 to 6 years of age was previously conducted and supported vaccine advancement to evaluation in younger children. Methods: Three seropositive children 1 to 2 years of age received a single intranasal dose of 5 × 105 EID50 SeV (SENDAI, Clinicaltrials.gov NCT00186927). Adverse events were collected for 28 days post-vaccine administration using diary cards and participants were followed for six months in total. Sera were collected longitudinally for clinical laboratory and virus-specific antibody tests. Nasal swabs were collected longitudinally for virus and mucosal antibody tests. Results: Intranasal SeV was well tolerated, with only mild grade 1–2 events that resolved spontaneously. No serious adverse events, medically attended adverse events, or adverse events causing protocol termination were reported. One participant had positive nasal swabs for inoculated SeV during the first week after vaccination. Although children had measurable PIV-1-specific serum antibodies at baseline, intranasal SeV vaccination resulted in significant serum antibody increases in all participants. Similarly, there were significant increases in PIV-1-specific nasal IgG and IgA levels in all participants. Elevated antibody levels persisted through the six months of follow-up. Conclusions: Intranasal SeV was well tolerated and uniformly immunogenic in seropositive children 1 to 2 years of age. Results encourage the further evaluation of SeV and SeV-based recombinants as potential intranasal vaccines for the prevention of infection by hPIV-1 and other serious respiratory pathogens. Full article
(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)
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15 pages, 1977 KiB  
Article
A Multi-Valent Hantavirus Vaccine Based on Recombinant Modified Vaccinia Ankara Reduces Viral Load in a Mouse Infection Model
by Marilyn Aram, Victoria Graham, Emma Kennedy, Emma Rayner, Roger Hewson and Stuart Dowall
Vaccines 2025, 13(3), 270; https://doi.org/10.3390/vaccines13030270 - 4 Mar 2025
Viewed by 894
Abstract
Background: Old World orthohantaviruses are the aetiological agent of Haemorrhagic Fever with Renal Syndrome (HFRS) disease. Worldwide, the two most prominent pathogens of HFRS are Seoul orthohantavirus (SEOV) and Hantaan orthohantavirus (HTNV). There is currently no specific treatment nor widely licensed vaccine [...] Read more.
Background: Old World orthohantaviruses are the aetiological agent of Haemorrhagic Fever with Renal Syndrome (HFRS) disease. Worldwide, the two most prominent pathogens of HFRS are Seoul orthohantavirus (SEOV) and Hantaan orthohantavirus (HTNV). There is currently no specific treatment nor widely licensed vaccine form hantaviruses. Methods: This study developed a virus-vectored vaccine approach using modified vaccinia Ankara (MVA) incorporating a SEOV-HTNV chimeric nucleoprotein antigen. Results: The vaccine demonstrated the induction of humoral and cellular immunity. In the absence of a disease model, a reduction in the viral load of a susceptible mouse strain with type-I interferon receptor deficiency (A129) was used to ascertain protective effects after challenge with SEOV. Results demonstrated a significant reduction in and/or clearance of viral RNA in immunised animals. Conclusions: An MVA viral vector vaccine incorporating the nucleoprotein as antigen offers a promising approach for Hantavirus vaccine development. Full article
(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)
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14 pages, 2638 KiB  
Article
Evaluating Antigen- and Vector-Specific Immune Responses of a Recombinant Pichinde Virus-Based Vaccine Expressing the Lymphocytic Choriomeningitis Virus Nucleoprotein
by Michaela Cain, Qinfeng Huang, Shania Sanchez, Hinh Ly and Yuying Liang
Vaccines 2024, 12(12), 1450; https://doi.org/10.3390/vaccines12121450 - 23 Dec 2024
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Abstract
Background: Live viral vector-based vaccines are known to elicit strong immune responses, but their use can be limited by anti-vector immunity. Here, we analyzed the immunological responses of a live-attenuated recombinant Pichinde virus (PICV) vector platform (rP18tri). Methods: To evaluate anti-PICV immunity in [...] Read more.
Background: Live viral vector-based vaccines are known to elicit strong immune responses, but their use can be limited by anti-vector immunity. Here, we analyzed the immunological responses of a live-attenuated recombinant Pichinde virus (PICV) vector platform (rP18tri). Methods: To evaluate anti-PICV immunity in the development of vaccine antigen-specific immune responses, we generated a rP18tri-based vaccine expressing the lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) and administered four doses of this rP18tri-NPLCMV vaccine to mice. Using MHC-I tetramers to detect PICV NP38-45 and LCMV NP396-404 epitope-specific CD8+ T cells, we monitored vector- and vaccine-antigen-specific immune responses after each vaccination dose. Results: LCMV NP396-404-specific effector and memory CD8+ T cells were detected after the first dose and peaked after the second dose, whereas PICV NP38-45-specific memory CD8+ T cells increased with each dose. PICV-binding IgG antibodies peaked after the second dose, while anti-PICV neutralizing antibodies (NAbs) remained low even after the fourth dose. Immunization with the rP18tri-NPLCMV vaccine significantly reduced LCMV viral titers in a chronic LCMV Clone 13 infection model, demonstrating the protective role of LCMV NP-specific T cells. Conclusion: These findings provide important insights into the antigen- and vector-specific immunity of the rP18tri-NPLCMV vaccine and support the development of NP-based vaccines against arenavirus pathogens. Full article
(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)
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20 pages, 2672 KiB  
Article
Construction and Characterization of a High-Capacity Replication-Competent Murine Cytomegalovirus Vector for Gene Delivery
by André Riedl, Denisa Bojková, Jiang Tan, Ábris Jeney, Pia-Katharina Larsen, Csaba Jeney, Florian Full, Ulrich Kalinke and Zsolt Ruzsics
Vaccines 2024, 12(7), 791; https://doi.org/10.3390/vaccines12070791 - 18 Jul 2024
Viewed by 1693
Abstract
We investigated the basic characteristics of a new murine cytomegalovirus (MCMV) vector platform. Using BAC technology, we engineered replication-competent recombinant MCMVs with deletions of up to 26% of the wild-type genome. To this end, we targeted five gene blocks (m01-m17, m106-m109, m129-m141, m144-m158, [...] Read more.
We investigated the basic characteristics of a new murine cytomegalovirus (MCMV) vector platform. Using BAC technology, we engineered replication-competent recombinant MCMVs with deletions of up to 26% of the wild-type genome. To this end, we targeted five gene blocks (m01-m17, m106-m109, m129-m141, m144-m158, and m159-m170). BACs featuring deletions from 18% to 26% of the wild-type genome exhibited delayed virus reconstitution, while smaller deletions (up to 16%) demonstrated reconstitution kinetics similar to those of the wild type. Utilizing an innovative methodology, we introduced large genomic DNA segments, up to 35 kbp, along with reporter genes into a newly designed vector with a potential cloning capacity of 46 kbp (Q4). Surprisingly, the insertion of diverse foreign DNAs alleviated the delayed plaque formation phenotype of Q4, and these large inserts remained stable through serial in vitro passages. With reporter-gene-expressing recombinant MCMVs, we successfully transduced not only mouse cell lines but also non-rodent mammalian cells, including those of human, monkey, bovine, and bat origin. Remarkably, even non-mammalian cell lines derived from chickens exhibited successful transduction. Full article
(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)
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Review

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18 pages, 974 KiB  
Review
Trends in Viral Vector-Based Vaccines for Tuberculosis: A Patent Review (2010–2023)
by Lana C. Santos, Antônio Márcio Santana Fernandes, Izabel Almeida Alves, Mairim Russo Serafini, Leandra da Silva e Silva, Humberto Fonseca de Freitas, Luciana C. C. Leite and Carina C. Santos
Vaccines 2024, 12(8), 876; https://doi.org/10.3390/vaccines12080876 - 2 Aug 2024
Viewed by 1958
Abstract
Tuberculosis (TB) is an ancient global public health problem. Several strategies have been applied to develop new and more effective vaccines against TB, from attenuated or inactivated mycobacteria to recombinant subunit or genetic vaccines, including viral vectors. This review aimed to evaluate patents [...] Read more.
Tuberculosis (TB) is an ancient global public health problem. Several strategies have been applied to develop new and more effective vaccines against TB, from attenuated or inactivated mycobacteria to recombinant subunit or genetic vaccines, including viral vectors. This review aimed to evaluate patents filed between 2010 and 2023 for TB vaccine candidates. It focuses on viral vector-based strategies. A search was carried out in Espacenet, using the descriptors “mycobacterium and tuberculosis” and the classification A61K39. Of the 411 patents preliminarily identified, the majority were related to subunit vaccines, with 10 patents based on viral vector platforms selected in this study. Most of the identified patents belong to the United States or China, with a concentration of patent filings between 2013 and 2023. Adenoviruses were the most explored viral vectors, and the most common immunodominant Mycobacterium tuberculosis (Mtb) antigens were present in all the selected patents. The majority of patents were tested in mouse models by intranasal or subcutaneous route of immunization. In the coming years, an increased use of this platform for prophylactic and/or therapeutic approaches for TB and other diseases is expected. Along with this, expanding knowledge about the safety of this technology is essential to advance its use. Full article
(This article belongs to the Special Issue Viral Vector-Based Vaccines and Therapeutics)
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