There is little information on relationships between indirect and direct protection by COVID-19 vaccination on close contacts of the vaccinees. Here, we assessed effect modification of direct-indirect action influencing the protective effects of vaccination. Secondary attack rates (SARs) in household contacts (n = 2422) depending on vaccination status of the index cases (n = 1112) with known vaccination history during the delta variant-dominant period (August 2-November 2, 2021) in two public health jurisdictions were calculated using multivariable logistic regression analysis to assess indirect protection by COVID-19 vaccination as adjusted odds ratios (aORs) for SARs. The impact of the time of index case vaccination on indirect-direct protective effects was also assessed. Contacts of index cases receiving 2× COVID-19 vaccinations showed significantly lower SARs than contacts of unvaccinated index cases (aOR:0.48, 95 %CI = 0.32-0.74). Relative to contacts where neither index cases nor contacts themselves were vaccinated (0,0), those with (2,0), (0,2) and (2,2) had lower SARs (0.45, 95 %CI = 0.24-0.82, 0.24, 95 %CI = 0.17-0.032, 0.11, 95 %CI = 0.06-0.20, respectively. No significant interactions on the SARs regarding times of vaccination between index cases and household contacts were observed, indicating additive but not synergistic protection. The indirect protective effects of COVID-19 vaccination were attributed to an additive effect together with the direct effect on onward transmission in the household setting. These findings emphasize the importance of herd immunity by COVID-19 vaccination not only for unvaccinated but also vaccinated individuals.

In February 2024, a 22-year-old Japanese resident of Osaka Prefecture was diagnosed with measles in the PCR test. He had flown from Dubai to Osaka Kansai International Airport. We finally detected 13 incident measles cases identified as infected by the index case and collected data on these individuals to evaluate the association between vaccination and incubation period. The mean incubation period in all 13 infectees was 11.7 days (range: 7-20 days). The incubation period among infectees who had no history of measles vaccination ranged from 7 to 10 days (mean: 8.4 days), whereas it was significantly longer in those who had received any measles vaccine (p = 0.005). Moreover, the number of measles vaccinations received correlated positively with the length of the incubation period (p = 0.004).

We assessed case fatality rates (CFRs) in cases aged ≥70 years in 10 Japanese prefectures (14.8 million residents) diagnosed between January 2022 and March 2023, when the Omicron variant was dominant in Japan. We selected incident reports on 283,052 study subjects from participating Public Health Centers adhering to the Infectious Diseases Control Law. Cases were passively followed up until the end of their isolation, date of death or 28 days after the COVID-19 diagnosis, whichever occurred first. We calculated age-standardized CFRs with 95% confidence intervals (CI) using the Japanese population aged 70-79, 80-89 and ≥90 in 2022 divided into 16 subgroups according to the period of COVID-19 diagnosis. The total overall CFR was 1.59% (95% CI 1.55-1.64); it ranged between 0.67% (95% CI 0.38-0.96, May 23-June 19) and 2.58% (95% CI 2.36-2.80, January 31-February 27). We observed three peaks of age-standardized CFRs paralleling the 6th, 7th and 8th endemic COVID-19 waves driven by Omicron in Japan (2.2% January 31-February 27, 1.0% July 18-August 14 and 1.6% December 26-January 22, 2023, respectively). Population-based CFRs for Omicron variant COVID-19 in Japanese aged ≥70 years remained <3% throughout the period January 2022-March 2023, including during three large endemic waves in this country.

Background: Limited information has been shown quantitatively assessed factors associated with the risk of secondary transmission in measles index cases.Method: We collected data on measles index cases reported in Osaka Prefecture between November 2018 and March 2019, along with their close contacts. Secondary attack rates (SARs) in contacts of index cases were calculated and compared depending on the vaccination status, classical or modified measles and other risk factors in index cases. For the multivariate analyses, we used binary logistic regression to adjust for these potential confounding factors on the secondary transmission and calculated the adjusted odds ratio (aOR) for the SARs.Result: A total of 105 index cases were included, involving 9,846 close contacts, with 72 secondary cases identified. A significant negative association between the number of vaccinations received by index cases and the risk of secondary infection in his/her close contacts (p < 0.01). Index cases who had received one vaccine dose had an aOR of 0.22 (95% CI: 0.08–0.65), while those with two or more doses had an aOR of 0.25 (95% CI: 0.07–0.85). Index cases who did not exhibit all three classic measles symptoms had a significantly lower risk of causing secondary infections compared to those who presented with all three symptoms (aOR: 0.12, 95% CI: 0.03–0.39).Conclusion: The indirect protective effect of measles vaccination would present important evidence supporting the further strengthening of vaccination policies.

Background: Multiple 3D culture models have been reported as a superior tumor model than 2D culture. The importance of interaction between cancer and stromal cells has been widely recognized in tumor progression and resistance to treatment. Therefore, ex vivo model recapturing the tumor microenvironment is needed to evaluate the drug efficacy under the condition imitating the patient tumor tissue. Purpose: We developed a unique 3D co-cultured tumor model with stromal tissues containing a microvascular network. Here, we investigated drug sensitivity in conventional 2D culture, our 3D co-cultured model and in vivo tumor. Methods: Drug sensitivity and gene expression on our model were evaluated using patient-derived cancer cells (PDC) established from colorectal cancer (CRC) patients in JFCR. The characteristics were compared with those of conventional 2D cultured cells or patient-derived xenograft (PDX). Results: In our 3D model, the drug sensitivities tended to be decreased in comparison with those of 2D. However, some drugs presented potent efficacy in our 3D model rather than 2D, and such drugs showed significant tumor growth suppression or tumor regression in vivo. Transcriptome profiles of our 3D model showed relatively higher similarity to those of in vivo tumors than those of 2D. Conclusion: Our study proposed the unique 3D co-cultured tumor model which may enable more accurate evaluation of drug sensitivities reflecting the in vivo circumstances. Citation Format: Yuki Takahashi, Shiro Kitano, Eiji Shinozaki, Satoshi Nagayama, Ryohei Katayama, Naoya Fujita. Layered 3D co-cultured tumor model including vascularized stromal tissue may reflect drug sensitivities in vivo tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6027.