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Objective: A first protective dose of vaccine may allow delaying the second dose in a context of low supply. The objective is to assess the effectiveness of a single dose of vaccine against SARS-CoV-2 (BNT162b2) after twelve days of its administration in healthcare personnel (HCP) of a Health Department., Methods: A case-control study was made. HCP with suspected COVID-19 and HCP close contacts of COVID-19 cases were included between January 27 and February 7, 2021. They were PCR tested for SARS-CoV-2; those with positive PCR were considered cases and those with negative PCR were considered controls. The crude (VE) and adjusted (VEa) vaccine effectiveness to prevent COVID-19 cases and their 95% confidence interval were calculated using the formula VE = (1-Odds ratio) x 100., Results: 268 HCP were included, of which 70 (26.1%) were considered cases and 198 (73.9%) controls. The frequency of vaccine exposure in cases was 55.7% vs. 69.7% in controls (p=0.035). The VEa of the first vaccine dose was 52.6% (95%CI: 1.1-77.3). The VEa in the subgroup of HCP studied for suspected disease was 74.6% (CI95%: 38.4-89.5)., Conclusions: One dose of BNT162b2 vaccine against SARS-CoV-2 offers early protection after twelve days of administration. These data could be considered to adapt strategies and consider postponing the second dose in situations of limited vaccine supply in order to achieve the maximum number of people covered with a first dose.

Integrase-defective lentiviral vectors (IDLVs) have been used as a safe and efficient delivery system in several immunization protocols in murine and non-human primate preclinical models as well as in recent clinical trials. In this work, we validated in preclinical murine models our vaccine platform based on IDLVs as delivery system for cancer immunotherapy. To evaluate the anti-tumor activity of our vaccine strategy we generated IDLV delivering ovalbumin (OVA) as a non-self-model antigen and TRP2 as a self-tumor associated antigen (TAA) of melanoma. Results demonstrated the ability of IDLVs to eradicate and/or controlling tumor growth after a single immunization in preventive and therapeutic approaches, using lymphoma and melanoma expressing OVA. Importantly, LV-TRP2 but not IDLV-TRP2 was able to break tolerance efficiently and prevent tumor growth of B16F10 melanoma cells. In order to improve the IDLV efficacy, the human homologue of murine TRP2 was used, showing the ability to break tolerance and control the tumor growth. These results validate the use of IDLV for cancer therapy.

Introduction: This study examines the frequency, associated factors, and characteristics of healthcare personnel coronavirus disease 2019 cases in a healthcare department that comprises a tertiary hospital and its associated 12 primary healthcare centers., Methods: This study included healthcare personnel that showed symptoms or were in contact with a coronavirus disease 2019 case patient from March 2, 2020 to April 19, 2020. Their evolution and characteristics (age, sex, professional category, type of contact) were recorded. Correlations between the different characteristics and risk of developing coronavirus disease 2019 and severe coronavirus disease 2019 were analyzed using chi-square tests. Their magnitudes were quantified with ORs, AORs, and their 95% CIs using a logistic regression model., Results: Of the 3,900 healthcare professionals in the department, 1,791 (45.9%) showed symptoms or were part of a contact tracing study. The prevalence of those with symptoms was 20.1% (784/3,900; 95% CI=18.8, 21.4), with coronavirus disease 2019 was 4.0% (156/3,900; 95% CI=3.4, 4.6), and with severe coronavirus disease 2019 was 0.5% (18/3,900; 95% CI=0.2, 0.7). The frequency of coronavirus disease 2019 in symptomatic healthcare personnel with a nonprotected exposure was 22.8% (112/491) and 13.7% (40/293) in those with a protected exposure (AOR=2.2, 95% CI=1.2, 3.9). The service in which the healthcare personnel performed their activity was not significantly associated with being diagnosed with coronavirus disease 2019. A total of 26.3% (10/38) of male healthcare personnel with coronavirus disease 2019 required hospitalization, compared with 6.8% (8/118) among female healthcare personnel (OR=4.9, 95% CI=1.8, 13.6)., Conclusions: A surveillance and monitoring program centred on healthcare personnel enables an understanding of the risk factors that lead to coronavirus disease 2019 among this population. This knowledge allows the refinement of the strategies for disease control and prevention in healthcare personnel during the coronavirus disease 2019 pandemic., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Lentiviruses are among the most promising viral vectors for in vivo gene delivery. To overcome the risk of insertional mutagenesis, integrase-deficient lentiviral vectors (IDLVs) have been developed. We show here that strong and persistent specific cytotoxic T cell (CTL) responses are induced by IDLVs, which persist several months after a single injection. These responses were associated with the induction of mild and transient maturation of dendritic cells (DCs) and with the production of low levels of inflammatory cytokines and chemokines. They were independent of the IFN-I, TLR/MyD88, interferon regulatory factor (IRF), retinoic acid induced gene I (RIG-I), and stimulator of interferon genes (STING) pathways but require NF-κB signaling in CD11c + DCs. Despite the lack of integration of IDLVs, the transgene persists for 3 months in the spleen and liver of IDLV-injected mice. These results demonstrate that the capacity of IDLVs to trigger persistent adaptive responses is mediated by a weak and transient innate response, along with the persistence of the vector in tissues., (Copyright © 2019 Institut Pasteur. Published by Elsevier Inc. All rights reserved.)

Viral vectors represent an attractive technology for vaccine delivery. We exploited the integrase defective lentiviral vector (IDLV) as a platform for delivering relevant antigens within the context of the ADITEC collaborative research program. In particular, Influenza virus hemagglutinin (HA) and nucleoprotein (NP) were delivered by IDLVs while H1N1 A/California/7/2009 subunit vaccine (HAp) with or without adjuvant was used to compare the immune response in a murine model of immunization. In order to maximize the antibody response against HA, both IDLVs were also pseudotyped with HA (IDLV-HA/HA and IDLV-NP/HA, respectively). Groups of CB6F1 mice were immunized intramuscularly with a single dose of IDLV-NP/HA, IDLV-HA/HA, HAp alone, or with HAp together with the systemic adjuvant MF59. Six months after the vaccine prime all groups were boosted with HAp alone. Cellular and antibody responses to influenza antigens were measured at different time points after the immunizations. Mice immunized with HA-pseudotyped IDLVs showed similar levels of anti-H1N1 IgG over time, evaluated by ELISA, which were comparable to those induced by HAp + MF59 vaccination, but significantly higher than those induced by HAp alone. The boost with HAp alone induced an increase of antibodies in all groups, and the responses were maintained at higher levels up to 18 weeks post-boost. The antibody response was functional and persistent overtime, capable of neutralizing virus infectivity, as evaluated by hemagglutination inhibition and microneutralization assays. Moreover, since neuraminidase (NA)-expressing plasmid was included during IDLV preparation, immunization with IDLV-NP/HA and IDLV-HA/HA also induced functional anti-NA antibodies, evaluated by enzyme-linked lectin assay. IFNγ-ELISPOT showed evidence of HA-specific response in IDLV-HA/HA immunized animals and persistent NP-specific CD8+ T cell response in IDLV-NP/HA immunized mice. Taken together our results indicate that IDLV can be harnessed for producing a vaccine able to induce a comprehensive immune response, including functional antibodies directed toward HA and NA proteins present on the vector particles in addition to a functional T cell response directed to the protein transcribed from the vector.