Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the SARS-CoV-2 Omicron BA.1 and BA.2 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: Evaluating COVID-19 vaccine effectiveness (VE) domestically is crucial for assessing and determining national vaccination policy. This study aimed to evaluate VE of mRNA COVID-19 vaccines in Japan. METHODS: We conducted a multicenter test-negative case-control study. The study comprised individuals aged ≥16 visiting medical facilities with COVID-19-related signs or symptoms from 1 January to 26 June 2022, when Omicron BA.1 and BA.2 were dominant nationwide. We evaluated VE of primary and booster vaccination against symptomatic SARS-CoV-2 infections and relative VE of booster compared with primary. RESULTS: We enrolled 7,931 episodes, including 3,055 test positive. The median age was 39, 48.0% were male, and 20.5% had underlying medical conditions. In individuals aged 16 to 64, VE of primary vaccination within 90 days was 35.6% (95% CI, 19.0-48.8%). After booster, VE increased to 68.7% (60.6-75.1%). In individuals aged ≥65, VE of primary and booster was 31.2% (-44.0-67.1%) and 76.5% (46.7-89.7%), respectively. Relative VE of booster compared with primary vaccination was 52.9% (41.0-62.5%) in individuals aged 16 to 64 and 65.9% (35.7-81.9%) in individuals aged ≥65. CONCLUSIONS: During BA.1 and BA.2 epidemic in Japan, mRNA COVID-19 primary vaccination provided modest protection. Booster vaccination was necessary to protect against symptomatic infections.

Effectiveness of Messenger RNA Coronavirus Disease 2019 Vaccines Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Delta Variant Epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines has been reported in studies in several countries, data are limited from Asian countries, especially against the Delta (B.1.617.2) variant. METHODS: We conducted a multicenter test-negative case-control study in patients aged ≥16 years visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from 1 July to 30 September 2021, when the Delta variant was dominant (≥90% of SARS-CoV-2 infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16-64 years was also assessed. RESULTS: We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving 2 doses ≥14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8%-93.9%) among patients aged 16-64 years and 90.3% (95% CI, 73.6%-96.4%) among patients aged ≥65 years. Among patients aged 16-64 years, vaccine effectiveness was 91.8% (95% CI, 80.3%-96.6%) within 1-3 months after full vaccination, and 86.4% (95% CI, 56.9%-95.7%) within 4-6 months. CONCLUSIONS: mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July-September 2021, when the Delta variant was dominant nationwide.

Pilot study of oncolytic viral therapy using mutant herpes simplex virus (HF10) against recurrent metastatic breast cancer.

BACKGROUND: An oncolytic herpes simplex virus type 1 mutant (HF10) has been isolated and evaluated for antitumor efficacy in a syngeneic immunocompetent mouse model, where it was effective against cancer and conferred resistance to rechallenge with tumor cells in all surviving mice. Several studies have shown that HF10 is effective and safe for use against localized or peritoneally disseminated nonneuronal malignant tumors in animals. METHODS: A pilot study using HF10 was initiated in six patients with cutaneous or subcutaneous metastases from breast cancer. For each patient, .5 mL of HF10 suspension containing various viral doses was injected into one nodule; .5 mL of sterile saline was injected into another. All patients were monitored for local and systemic adverse effects. Nodules were excised 14 days after injection for histopathologic studies. RESULTS: All patients tolerated the intratumoral injection of HF10. No adverse effects occurred, and histopathological evaluation revealed 30% to 100% cancer cell death. CONCLUSIONS: This pilot study found HF10 to be safe and effective against metastatic breast cancer.

[Novel treatment with oncolytic herpes simplex virus, 'HF10' against breast cancer].

An oncolytic herpes simplex virus type 1 mutant, named HF10, has been isolated and evaluated for anti-tumor efficacy in syngeneic immuno-competent mouse models. We have found that the mutant virus can very effectively treat cancer, and that all of survived mice acquire resistance to rechallenge of the tumor cells. Since a number of studies have shown that HF10 is effective and safe for use in localized or peritoneally disseminated malignant tumors of non-neuronal origin, phase I/II clinical trials using HF10 have been initiated for patients with metastatic breast cancer. Preliminary data from the clinical trials are encouraging.

Oncolytic viral therapy for breast cancer with herpes simplex virus type 1 mutant HF 10.

BACKGROUND AND OBJECTIVES: Many genetically engineered viruses have been evaluated for their potential as therapeutic agents in the treatment of malignant tumors. We applied a spontaneously generated, highly attenuated herpes simplex virus (HSV) type-1 clone, HF10, to the treatment of breast cancer. In this study, we investigated the ability of HF10 to infect and lyse human and murine breast cancer cells in vitro and tested its efficacy in an immuno-competent animal model of breast cancer. METHODS: To assess the therapeutic efficacy of HF10 against subcutaneous tumors in vivo, mouse breast cancer cells were injected into the backs of mice, which were then treated with HF10. Tumor volume and survival rate were used as measures of the antitumor effect in the in vivo experiments. In vitro viral cytotoxity assays and replication assays were also performed in human breast cancer cell lines. RESULTS: In the in vivo study, tumor growth was suppressed and long-term survival rates were prolonged. HF10 was effective in producing cytolytic effects in vitro at various multiplicities of infection (MOI) in all cell lines tested. CONCLUSIONS: HF10 demonstrated antitumor effects in our animal model. The viral growth and oncolytic effect of HF10 in the human breast cancer cell line suggest that HF10 is potentially effective in the clinical treatment of human cancer. These results indicate that replication-competent HSV-1 mutants hold significant promise as cancer therapeutic agents.

Effective treatment of disseminated peritoneal colon cancer with new replication-competent herpes simplex viruses.

BACKGROUND/AIMS: Oncolytic herpes simplex virus type 1 mutants are promising therapeutic agents for malignant tumors. Their efficacy depends on the extent of both viral replication in the tumor and induction of a host anti-tumor immune response. In this study, new replication-competent, attenuated herpes simplex virus mutants, named HF10 and Hh101, have been evaluated for their oncolytic activities. METHODOLOGY: We determined the genome structures of the mutants and examined the survival rates of mice that were injected intraperitoneally with carcinoma and sarcoma cells and treated with the mutants. Tumors were examined by both histology and immunochemistry. RESULTS: HF10 and Hh101 administration effectively treated disseminated peritoneal colon carcinoma in a BALB/c mouse model and all surviving mice were resistant to rechallenge of the tumor cells. The survival rate in a C3H mouse model was improved by HF10, but not Hh101. CONCLUSIONS: HF10 and Hh101, novel agents as oncolytic viral therapy, are both safe and effective herpes simplex virus mutants for malignant tumor treatment. The Hh101, is more attenuated in its virulence than the HF10 because it is a double gene knocking-out construct. The choice of viral mutant for treatment should be made according to the type of malignancy.