Project description:In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulate a potent cytotoxic T cells immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma (HCC) and colorectal cancer (CRC).
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
Project description:Oncolytic viral therapy is an emerging new class of immunotherapy that involves selectively infecting and killing tumor cells. Several oncolytic viruses (OVs) have exhibited promising potential for treating human cancer in animal models and clinical trials, including hepatocellular carcinoma (HCC). However, despite clinical evidence and benefit for patients, the cost-intensive manufacturing and testing nature of oncolytic viral products makes them far out of reach for most US patients. We propose to develop a cost-effective immunovirotherapy approach that could synergize with other therapies to improve the outcomes for patients with advanced HCC. Specifically, we showed that intratumoral administration of low doses of the live attenuated measles, mumps and rueball viruses (MMR) vaccine effectively activates a robust cytotoxic T cells response, leading to tumor regression and extended survival in the syngeneic HCC model. Using transcriptomic approach, we showed that mechanistically MMR exerts its anti-tumor activity by priming innate and adaptive anti-tumor immune responses, leading to immunologically coordinated death of cancer cells. The proposed research can impact cancer patients globally, and our multidisciplinary team is uniquely equipped to execute the proposed studies.
Project description:Blood collected from adults pre vaccination and post vaccination to study the immune effects of COVID-19 vaccination and how they relate to antibody and T-cell responses.