The Cat Que orthobunyavirus has been found in mosquitoes, birds, pigs, and humans, suggesting its wide range of hosts and potential public health implications. During arbovirus surveillance in 2013, the HN1304M virus was isolated from naturally occurring Culicoides biting midges in Hunan Province, southern China. The virus was cytopathic to BHK-21 cells and showed stable passage, but was not cytopathic to C6/36 cells. Determination and analysis of the viral genome sequence revealed that HN1304M is an RNA virus with three gene segments, namely, L, M, and S. The nucleotide and amino acid sequence homologies of HN1304M to Cat Que viruses in the Manzanilla species complex were 90.3–99.4%, and 95–100%, respectively, while the homologies to other viruses in this species complex were 74–86.6% and 78.1–96.1%, respectively. A phylogenetic analysis of the viral genes revealed that HN1304M formed an evolutionary branch with other Cat Que viruses isolated from mosquitoes, pigs, birds, and humans, which was completely independent of the other viruses in this complex. The fact that the Cat Que virus was isolated from Culicoides suggests that biting midges may participate in the natural circulation of Cat Que viruses.

Human respiratory syncytial virus (HRSV) poses a significant disease burden on global health. To date, two vaccines that primarily induce humoral immunity to prevent HRSV infection have been approved, whereas vaccines that primarily induce T-cell immunity have not yet been well-represented. To address this gap, 25 predicted T-cell epitope peptides derived from the HRSV fusion protein with high human leukocyte antigen (HLA) binding potential were synthesized, and their ability to be recognized by PBMC from previously infected HRSV cases was assessed using an ELISpot assay. Finally, nine T-cell epitope peptides were selected, each of which was recognized by at least 20% of different donors’ PBMC as potential vaccine candidates to prevent HRSV infection. The protective efficacy of F-9PV, a combination of nine peptides along with CpG-ODN and aluminum phosphate (Al) adjuvants, was validated in both HLA-humanized mice (DR1-TCR transgenic mice, Tg mice) and wild-type (WT) mice. The results show that F-9PV significantly enhanced protection against viral challenge as evidenced by reductions in viral load and pathological lesions in mice lungs. In addition, F-9PV elicits robust Th1-biased response, thereby mitigating the potential safety risk of Th2-induced respiratory disease during HRSV infection. Compared to WT mice, the F-9PV mice exhibited superior protection and immunogenicity in Tg mice, underscoring the specificity for human HLA. Overall, our results demonstrate that T-cell epitope peptides provide protection against HRSV infection in animal models even in the absence of neutralizing antibodies, indicating the feasibility of developing an HRSV T-cell epitope peptide-based vaccine.

The authors would like to make the following corrections to this published paper