Homologous and heterologous booster vaccinations of S-268019-b, a recombinant S protein-based vaccine with a squalene-based adjuvant, enhance neutralization breadth against SARS-CoV-2 Omicron subvariants in cynomolgus macaques.

SARS-CoV-2 Omicron subvariants such as BA.2.12.1, BA.4 and BA.5 have been spreading rapidly and become dominant worldwide. Here we report the homologous or heterologous booster effects of S-268019-b, a recombinant spike protein vaccine with the squalene-based adjuvant A-910823 in cynomolgus macaques. In macaques which had been primed with S-268019-b or mRNA vaccines, boosting with S-268019-b enhanced neutralizing antibodies (NAb) against ancestral SARS-CoV-2. Since boosting with the antigen without adjuvant did not efficiently restore NAb titers, adjuvant A-910823 was essential for the booster effect. Importantly, boosting with S-268019-b enhanced NAb against all of the Omicron subvariants we tested, including BA.2.12.1, BA.4 and BA.5, in comparison to two vaccine doses. Additionally, expansion of Omicron-specific B cells was confirmed after boosting with S-268019-b. These results indicate that a booster dose of S-268019-b with the adjuvant enhances the neutralization breadth.

Effects of radiation based on whole-body irradiation in HTLV-1-infected mice.

Adult T-cell leukemia is one of the life-threatening diseases that occur in individuals infected with human T-cell leukemia virus type 1 (HTLV-1). Clinical trials of hematopoietic stem cell transplantation therapy are being performed in addition to chemotherapy; however, neither is satisfactory. As a pretreatment for transplantation, anticancer drugs or whole-body irradiation is used to decrease the number of HTLV-1-infected cells, but there are numerous side effects. Therefore, in the present study, using a mouse model of HTLV-1 infection, the long-term survival and number of infected cells in the reservoir organ were investigated in order to determine the effect of γ-irradiation on HTLV-1-infected mice in vivo. There was no improvement in the survival period following γ-irradiation in the γ-irradiated group after HTLV-1 infection when compared with the HTLV-1-infected group. It was also found that the incidence of splenomegaly was ≥80% in the HTLV-1-infected and γ-irradiated group, which was significantly higher than that in the HTLV-1-infected mice. The tissue morphology in the spleen became non-uniform because of γ-rays. Importantly, the number of infected cells in the spleen was increased 4.1-fold in the HTLV-1-infected and γ-irradiated mice compared with that in the HTLV-1-infected mice. Careful consideration might be necessary when using whole-body irradiation in patients with HTLV-1 infection.

Clonal proliferation of HTLV-1-infected cells is associated with spontaneous malignant tumor formation in mice.

Adult T-cell leukemia/lymphoma (ATL) is characterized by monoclonal proliferation of tumor cells that harbor integrated human T-cell leukemia virus type-1 (HTLV-1). These malignant cells accumulate in various organs including the liver, spleen and skin in addition to blood and lymph nodes. Although there have been several reports of animal models of HTLV-1 infection in which proviral distribution has been examined, clonal expansion of the experimentally infected host cells has not been extensively analyzed. Here we provide experimental evidence that clonal proliferation of the infected host cells occurs in the spleen for more than one year. During a 15 month period of persistent infection, two out of ten mice developed spontaneous tumors. Although the tumors were not ATL-like, cells exhibiting mono- or oligoclonal proliferation and having the same site of HTLV-1 integration were identified in tumor tissues as well as in the spleen. Quantitative analysis of the cells belonging to each cell clone suggested that these proliferating cell clones were associated with the tumors and that spontaneous tumor tissues might provide a suitable microenvironment for proliferation and accumulation of infected cell clones at the late stage of infection.