Development of an attenuated smallpox vaccine candidate: The KVAC103 strain

Lim, Heeji; In, Hyun Ju; Kim, You-Jin; Lee, Yun Ha; Kim, Su Hwan; Lee, Sun Hwa; Park, Jun Hyuk; Yang, Haeryong; Yoo, Jung-Sik; Lee, Sang‐Won; Kim, Mi Young; Chung, Gyung Tae; Yeo, Sang Gu

doi:10.1016/j.vaccine.2021.06.060

Cited by 8 publications

(10 citation statements)

References 42 publications

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“…This attenuated phenotype might be due to two major deletions in the parental strain, resulting in twenty-three deleted and four truncated genes. 60 Recently, a KVAC103-based vaccine candidate against anthrax and smallpox expressing one of the major components of anthrax toxin (protective antigen, PA), termed KVAC103-thPA, induced binding and neutralizing antibodies against PA in mouse models. 61 Moreover, co-immunization with KVAC103 expressing IL-15 or the immunoadjuvant cholera toxin subunit A1 (CTA1) enhanced the immune response to protective levels after a challenge with Bacillus anthracis spores.…”

Section: Poxvirus-based Vaccines: From Variolation To Fourth-generati...mentioning

confidence: 99%

Highly Attenuated Poxvirus-Based Vaccines Against Emerging Viral Diseases

Perdiguero

Pérez

Marcos-Villar

et al. 2023

Journal of Molecular Biology

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Section: Poxvirus-based Vaccines: From Variolation To Fourth-generati...mentioning

confidence: 99%

Highly Attenuated Poxvirus-Based Vaccines Against Emerging Viral Diseases

Perdiguero

Pérez

Marcos-Villar

et al. 2023

Journal of Molecular Biology

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“…KVAC103, an innovative third-generation smallpox vaccine candidate, was developed using the Lancy-Vaxina strain [14]. This candidate has demonstrated a reduction in virulence and an augmentation in immune response, evidenced by elevated levels of neutralizing antibodies and IFNγ production in murine and rabbit models.…”

Section: Introductionmentioning

confidence: 99%

“…This candidate has demonstrated a reduction in virulence and an augmentation in immune response, evidenced by elevated levels of neutralizing antibodies and IFNγ production in murine and rabbit models. Genomic analysis identified significant deletions compared with the progenitor strain, indicating an enhancement in both the safety and efficacy profiles of KVAC103, making it a viable candidate for smallpox vaccination [14]. Concurrently, research efforts have focused on using attenuated vaccinia virus vectors to develop vaccines against infectious diseases and therapeutic vaccines for cancer [15,16].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Immunogenicity of rKVAC85B in a BCG Prime-Boost Regimen Against H37Rv and HN878 Tuberculosis Strains

Shin,

Yun,

Lee

et al. 2024

Preprint

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Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

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“…To improve the safety profile, newer generations of smallpox vaccines have been developed, but not deployed 17 – 19 . Researchers have recently sought to attenuate live VACVs and deliver them by microneedles 20 , 21 . Although safety profile improved with these attempts, public concerns about safety associated with live viruses is unlikely to have changed.…”

Section: Introductionmentioning

confidence: 99%

Evaluating immunogenicity of pathogen-derived T-cell epitopes to design a peptide-based smallpox vaccine

Quach

Ovsyannikova

Kennedy

2022

Sci Rep

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Despite the eradication in 1980, developing safe and effective smallpox vaccines remains an active area of research due to the recent outbreaks and the public health concern that smallpox viruses could be used as bioterrorism weapons. Identifying immunogenic peptides (epitopes) would create a foundation for the development of a robust peptide-based vaccine. We previously identified a library of naturally-processed, human leukocyte antigen class I-presented vaccinia-derived peptides from infected B cells. In the current study, we evaluated the immunogenicity of these T-cell peptides in both transgenic mouse models and human peripheral blood mononuclear cells. A vaccine based on four selected peptides provided 100% protection against a lethal viral challenge. In addition, responses from memory T cells remained unchanged up to five months. Our results validate a practical approach for identifying and verifying immunogenic peptides for vaccine development and highlight the potential of peptide-based vaccines for various infectious diseases.

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Development of an attenuated smallpox vaccine candidate: The KVAC103 strain

Cited by 8 publications

References 42 publications

Highly Attenuated Poxvirus-Based Vaccines Against Emerging Viral Diseases

Highly Attenuated Poxvirus-Based Vaccines Against Emerging Viral Diseases

Efficacy and Immunogenicity of rKVAC85B in a BCG Prime-Boost Regimen Against H37Rv and HN878 Tuberculosis Strains

Evaluating immunogenicity of pathogen-derived T-cell epitopes to design a peptide-based smallpox vaccine

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