Immunogenicity and Tolerability of a SARS-CoV-2 TNX-1800, a Live Recombinant Poxvirus Vaccine Candidate, in Syrian Hamsters and New Zealand White Rabbits

Awasthi, Mayanka; Macaluso, Anthony; Goebel, Scott J.; Luea, Erin; Noyce, Ryan S.; Nasar, Farooq; Daugherty, Bruce; Bavari, Sina; Lederman, Seth

doi:10.3390/v15102131

Cited by 2 publications

(3 citation statements)

References 14 publications

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“…The poxvirus vectors show great potential to address existing limitations and contribute to achieving global vaccination goals. Previously, we demonstrated the tolerability, safety, and immunogenicity of TNX-1800 in two animal models, Syrian hamsters and New Zealand white rabbits [21]. In the current report based on two NHP models, we confirm the immunogenicity and efficacy of TNX-1800, a live virus recombinant poxvirus vaccine candidate, against the SARS-CoV-2 challenge.…”

Section: Discussionsupporting

confidence: 77%

“…In addition, a single dose vaccination with TNX-801 was able to generate strong immunity and provided complete protection against lethal MPXV clade I challenge in NHPs [20]. Following successful NHP studies against MPXV, the TNX-801 platform was engineered to express the SARS-CoV-2 spike protein of the Wuhan strain (TNX-1800) [21]. TNX-1800 was well tolerated and immunogenic, and the vaccine didn't cause any disseminated horsepox infection in Syrian golden hamsters and New Zealand white rabbits [21].…”

Section: Introductionmentioning

confidence: 99%

“…Following successful NHP studies against MPXV, the TNX-801 platform was engineered to express the SARS-CoV-2 spike protein of the Wuhan strain (TNX-1800) [21]. TNX-1800 was well tolerated and immunogenic, and the vaccine didn't cause any disseminated horsepox infection in Syrian golden hamsters and New Zealand white rabbits [21].…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, against SARS-CoV-2 Challenge in Nonhuman Primates

Awasthi,

Macaluso,

Myscofski

et al. 2023

Vaccines

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TNX-1800 is a synthetically derived live recombinant chimeric horsepox virus (rcHPXV) vaccine candidate expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated with no serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding of anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In addition, a single dose of TNX-1800 induced an interferon-gamma (IFN-γ)-mediated T-cell response in Cynomolgus Macaques. Following challenge with SARS-CoV-2, African Green and Cynomolgus Macaques exhibited rapid clearance of virus in the upper and lower respiratory tract. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, against SARS-CoV-2 Challenge in Nonhuman Primates

Awasthi,

Macaluso,

Myscofski

et al. 2023

Vaccines

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Recombinant chimeric horsepox virus (TNX-801) is attenuated relative to vaccinia virus strains in both in vitro and in vivo models

Trefry,

Awasthi,

Raney

et al. 2024

mSphere

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Recombinant chimeric horsepox virus (TNX-801) is a preclinical vaccine in development against mpox and smallpox. In this report, we investigated the potential phenotypic differences in in vitro and in vivo models between TNX-801 and older vaccinia virus (VACV)-based vaccine strains (VACV-Lis and VACV-NYCBH) used in the eradication of smallpox as well as VACV-WR, VACV-IHD, and MVA. TNX-801 displayed a small plaque phenotype (~1–2 mm) in BSC-40 and Vero-E6 cells. Multi-step replication kinetics in immortalized nonhuman primate cell lines, and human primary cells from dermal and respiratory tracts yielded >10- to 100-fold lower infectious titers than the VACV strains. In addition, the infectious particle-to-genome copy ratio data suggests that TNX-801 genome packaging is ~10- to 100-fold less efficient than the VACV strains and the potential mechanism of TNX-801 attenuation is at the packaging/egress stage. Lastly, the susceptibility to VACV and TNX-801 infection of three new immunocompromised murine models (C56BL/6 Ifnar −/− , C56BL/6 Ifngr −/− , and C56BL/6 Ifnar −/− / Ifngr −/− ) was investigated. VACV strains were able to produce severe disease including decrease in body weight and temperature, as well as lethality in murine models via the intraperitoneal or intranasal routes. In contrast to VACV strains, TNX-801 was unable to produce any disease in murine models. These data demonstrate that TNX-801 is >10- to 1,000-fold more attenuated compared to older VACV-based smallpox vaccine strains in human primary cell lines and immunocompromised mice. IMPORTANCE Variola and monkeypox viruses are medically important pathogens that can cause fatal human disease. The two FDA-approved vaccines, ACAM-2000 and JYNNEOS, have important advantages and disadvantages. ACAM-2000 offers durable immunity; however, it has high adverse event rates. In contrast, JYNNEOS has a safer profile but requires two doses 4-weeks apart to achieve comparable immunity. Consequently, there is a need for vaccines offering durable immunity via single immunization with minimal adverse events. TNX-801 is a preclinical stage vaccine that can stimulate potent immunity via a single dose and provides protection against lethal mpox disease in the nonhuman primate model. Here, we show that TNX-801 is >10- to 1,000-fold attenuated in in vitro and in vivo models including human primary cells and immunocompromised murine models than vaccine strains utilized in smallpox eradication. The natural attenuation of TNX-801 and its ability to induce protective immunity via a single vaccination are promising and warrants further development.

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Immunogenicity and Tolerability of a SARS-CoV-2 TNX-1800, a Live Recombinant Poxvirus Vaccine Candidate, in Syrian Hamsters and New Zealand White Rabbits

Cited by 2 publications

References 14 publications

Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, against SARS-CoV-2 Challenge in Nonhuman Primates

Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, against SARS-CoV-2 Challenge in Nonhuman Primates

Recombinant chimeric horsepox virus (TNX-801) is attenuated relative to vaccinia virus strains in both in vitro and in vivo models

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