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Engineered chimeric antigen receptors (CARs) that are expressed in cytotoxic T cells and natural killer (NK) cells have been used to specifically target tumor cells. However, CAR-T and CAR-NK cells are still subject to down regulation by their inhibitory receptors after injection into patients.

SARS-CoV-2 has emerged as a global pathogen, sparking urgent vaccine development efforts. The trimeric SARS-CoV-2 spike appears to be a leading vaccine antigen. However, the inability of antibodies such as CR3022, which binds tightly to a cryptic spike epitope, to neutralize SARS-CoV-2 suggests a spike-based means of neutralization escape.

Malaria is a major disease caused by a parasite transmitted through the bite of infected female mosquitoes. Globally, an estimated 214 million cases of malaria and 438,000 deaths from malaria occur annually, with chidren in African and South Asian regions being most vulnerable. Approximately 1,500-2,000 cases of malaria are reported in the United States each year, mostly in returning travelers from malaria- endemic countries.

Human metapneumovirus (hMPV) infections have been shown as a common cause of upper and lower respiratory diseases such as bronchiolitis and pneumonia in young children, the elderly, and other immunocompromised individuals. Studies show that infections by the non-segmented negative strand RNA virus begin with attachment and entry of viral glycoproteins that mediate fusion with host cellular membranes. Like for the human respiratory syncytial virus (hRSV), a viral entry is initiated by the fusion (F) protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of for coronavirus disease 2019 (COVID-19). COVID-19 is characterized by fever, cough, difficulty breathing, loss of taste and smell, nausea, and sore throat. As of the fourth quarter 2020, COVID-19 is responsible for over 1.17 million deaths worldwide. As the pandemic continues to surge, the importance of a safe, affordable, and efficacious vaccine is of urgent importance.

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis and is associated with nearly 200,000 cancers and 140,000 deaths each year. EBV-associated cancers include Hodgkin's lymphoma, non-Hodgkin's lymphoma, Burkitt B cell lymphoma, and EBV post-transplant lymphoproliferative disease. The latent reservoir for EBV in the body is the B lymphocyte. Thus, blocking B cell infection is important for reducing EBV-related disease.

RSV is the most important viral agent of severe respiratory disease in infants and young children worldwide and also causes substantial morbidity and mortality in older adults. RSV is estimated to cause more than 33 million lower respiratory tract illnesses, three million hospitalizations, and nearly 200,000 childhood deaths worldwide annually, with many deaths occurring in developing countries. However, despite the prevalence of RSV and the dangers associated with infection, no RSV vaccine has been successfully developed to date.

SARS-CoV-2 has resulted in a global pandemic, sparking urgent vaccine development efforts. The trimeric SARS-CoV-2 spike stabilized in its prefusion conformation by the addition of 2 proline mutations (“SARS-CoV-2 S2P”) is the antigenic basis of SARS-CoV-2 vaccines that are currently authorized for use in the United States.

Vaccines for SARS-CoV-2 are increasingly available under emergency use authorizations; however, indications are currently limited to individuals twelve (12) years or older. They also involve intramuscular immunization, which does not directly stimulate local immunity in the respiratory tract, the primary site of SARS-CoV-2 infection, shedding and spread. While the major burden of COVID-19 disease is in adults, infection and disease also occur in infants and young children, contributing to viral transmission.

Human respiratory syncytial virus (RSV) continues to be the leading viral cause of severe acute lower respiratory tract disease in infants and children worldwide, and also is an important cause of morbidity and mortality in the elderly. A licensed vaccine or antiviral drug suitable for routine use remains unavailable. This invention relates to the use of murine pneumonia virus (MPV—previously known as pneumonia virus of mice, PVM—of family Pneumovirida e) as a vaccine vector expressing the RSV fusion protein F, the most important protective antigen of RSV.