Evaluation of new adjuvants in enhancing the immune response to a candidate of Severe Fever with Thrombocytopenia Syndrome Virus vaccine.
- 1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne bunyavirus SFTSV. SFTSV is primarily transmitted by Haemaphysalis longicornis ticks and can cause a hemorrhagic fever-like illness characterized by high fever, thrombocytopenia, leukopenia, and multiorgan failure, with reported case-fatality rates ranging from 10% to over 30%. Despite its growing public health relevance, no licensed vaccines or specific antiviral therapies are currently available. Here, we evaluated a beta-propiolactone-inactivated SFTSV vaccine candidate based on strain YL1, formulated with benchmark adjuvants (Addavax and Alhydrogel) or experimental innate immune agonists, including Sendai virus-derived defective interfering RNA (SDI), a RIG-I agonist, and imidazoquinoline-poly(ethylene glycol)-cholesterol conjugate (IMDQ-P-C), a TLR7/8 agonist, alone or in combination. Using an extended prime-boost regimen, we examined adjuvant-dependent modulation of humoral immunity, antigen-specific cellular recall, antibody cross-reactivity, and functional protection following passive serum transfer and live-virus challenge in IFNAR-/- mice. All adjuvanted formulations induced detectable humoral responses, with Addavax and SDI eliciting the highest virus-specific binding and neutralizing antibody titers. Antigen-specific analyses identified the nucleoprotein (NP) as the dominant target of vaccine-induced immune memory. NP elicited robust antibody response and the broadest cytokine recall profile following ex vivo stimulation. This response was broader than that induced by the whole inactivated virus and was characterized by mixed Th1-associated, Th2-associated, and proinflammatory-associated features that varied across adjuvant formulations. In contrast, the head domain of the Gn glycoprotein elicited limited cellular recall responses, consistent with its relatively weak humoral immunogenicity after both priming and boosting. Nevertheless, sera from SDI and Addavax-adjuvanted groups displayed cross-reactivity with Gn from a heterologous SFTSV strain, suggesting broader antibody recognition across viral genotypes. Functionally, sera from SDI and Addavax-immunized mice conferred partial protection following passive transfer into IFNAR-/- recipients, as reflected by reduced viral loads, delayed disease onset, and prolonged survival after lethal SFTSV challenge. Together, these findings support the immunogenicity and protective potential of a BPL-inactivated SFTSV vaccine platform and identify NP as a major target of vaccine-induced immune memory. They further highlight the importance of adjuvant selection in shaping the magnitude, antigenic focus, and functional quality of vaccine-induced antiviral immunity.
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BibTeX
@misc{levican2026evaluation,
title = {{Evaluation of new adjuvants in enhancing the immune response to a candidate of Severe Fever with Thrombocytopenia Syndrome Virus vaccine.}},
author = {J. A. Levican and N. Ferressini Gerpe and S.-C. Park and M. Noureddine and F. El-Ayache and V. Yan and L. Gruneberg and M. Prellberg and L. A. Chang and G. Laghlali and G. Singh and P. T. Wong and A. Levican and G. Palacios and A. Garcia-Sastre and M. Schotsaert},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.750931},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.750931v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Evaluation of new adjuvants in enhancing the immune response to a candidate of Severe Fever with Thrombocytopenia Syndrome Virus vaccine.
AU - J. A. Levican
AU - N. Ferressini Gerpe
AU - S.-C. Park
AU - M. Noureddine
AU - F. El-Ayache
AU - V. Yan
AU - L. Gruneberg
AU - M. Prellberg
AU - L. A. Chang
AU - G. Laghlali
AU - G. Singh
AU - P. T. Wong
AU - A. Levican
AU - G. Palacios
AU - A. Garcia-Sastre
AU - M. Schotsaert
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.750931
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.750931v1
AB - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne bunyavirus SFTSV. SFTSV is primarily transmitted by Haemaphysalis longicornis ticks and can cause a hemorrhagic fever-like illness characterized by high fever, thrombocytopenia, leukopenia, and multiorgan failure, with reported case-fatality rates ranging from 10% to over 30%. Despite its growing public health relevance, no licensed vaccines or specific antiviral therapies are currently available. Here, we evaluated a beta-propiolactone-inactivated SFTSV vaccine candidate based on strain YL1, formulated with benchmark adjuvants (Addavax and Alhydrogel) or experimental innate immune agonists, including Sendai virus-derived defective interfering RNA (SDI), a RIG-I agonist, and imidazoquinoline-poly(ethylene glycol)-cholesterol conjugate (IMDQ-P-C), a TLR7/8 agonist, alone or in combination. Using an extended prime-boost regimen, we examined adjuvant-dependent modulation of humoral immunity, antigen-specific cellular recall, antibody cross-reactivity, and functional protection following passive serum transfer and live-virus challenge in IFNAR-/- mice. All adjuvanted formulations induced detectable humoral responses, with Addavax and SDI eliciting the highest virus-specific binding and neutralizing antibody titers. Antigen-specific analyses identified the nucleoprotein (NP) as the dominant target of vaccine-induced immune memory. NP elicited robust antibody response and the broadest cytokine recall profile following ex vivo stimulation. This response was broader than that induced by the whole inactivated virus and was characterized by mixed Th1-associated, Th2-associated, and proinflammatory-associated features that varied across adjuvant formulations. In contrast, the head domain of the Gn glycoprotein elicited limited cellular recall responses, consistent with its relatively weak humoral immunogenicity after both priming and boosting. Nevertheless, sera from SDI and Addavax-adjuvanted groups displayed cross-reactivity with Gn from a heterologous SFTSV strain, suggesting broader antibody recognition across viral genotypes. Functionally, sera from SDI and Addavax-immunized mice conferred partial protection following passive transfer into IFNAR-/- recipients, as reflected by reduced viral loads, delayed disease onset, and prolonged survival after lethal SFTSV challenge. Together, these findings support the immunogenicity and protective potential of a BPL-inactivated SFTSV vaccine platform and identify NP as a major target of vaccine-induced immune memory. They further highlight the importance of adjuvant selection in shaping the magnitude, antigenic focus, and functional quality of vaccine-induced antiviral immunity.
ER -