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Nipah virus is an emerging pathogenic paramyxovirus responsible for sporadic and isolated outbreaks of severe respiratory and neurologic disease in Southern Asia. As a zoonotic virus, disease can manifest in both animals and human with indigenous fruit bats acting as natural reservoirs of the virus. The effects of viral infection vary from acute respiratory distress to fatal encephalitis.

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.

Ebola virus infection can lead to severe hemorrhagic fever, known as Ebola virus disease (EVD), which is often fatal. The Zaire species of Ebola virus (EBOV) was responsible for the largest Ebola outbreak in history, which occurred in 2014. Scientists at the NIAID Vaccine Research Center have developed a human monoclonal neutralizing antibody, mAb114 for treatment and prevention of EBOV infection. Because there are very few treatments available to treat or prevent EBOV infection, there is a great need to develop effective pre- and post- exposure therapeutics before another outbreak occurs.

The invention, a stabilized recombinant prefusion F protein (pre F), is a candidate subunit vaccine for Respiratory Syncytial Virus (RSV). Pre-F is stabilized in the prefusion conformation and displays epitopes not present in postfusion F protein. Several potent RSV neutralizing antibodies bind pre F, but not postfusion F. Therefore, immunization with pre F may elicit an immune response superior to the response generated by postfusion F.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is the primary target of neutralizing antibodies. The F glycoprotein exists in at least two conformations, a meta-stable prefusion state, and an extremely stable postfusion state. Both states share several epitopes targeted by neutralizing antibodies, but it has been demonstrated that the prefusion conformation of F contains at least one epitope not present in the postfusion conformation.

Human metapneumovirus (hMPV), a negative, single-stranded RNA virus, accounts for approximately 5-15% of infant respiratory tract infections and poses a severe risk of disease and hospitalization in both the elderly and the immunocompromised. Investigators at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) have generated an hMPV fusion glycoprotein (“F protein”) stabilized in a prefusion conformation.

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.

The invention provides immunogen polypeptides comprising fragments of VAR2CSA protein expressed by P. falciparum as potential second-generation placental malaria vaccine candidates. VAR2CSA is the leading antigen target for a placental malaria vaccine, where associated antibody titers are correlated with protection. Aspects of the inventive immunogen polypeptides comprise all or portions of the chondroitin sulfate A (CSA) binding regions of VAR2CSA, as identified by a structural study of VAR2CSA conducted by the inventors, that possess great sequence conservation among P.

Using a computational design methodology, SARS-CoV-2 spike proteins containing engineered amino acid changes to the receptor binding domain (RBD) were designed. These engineered spike proteins improved the immune response upon immunization of animals. An engineered RBD was also expressed at greater yield, had increased temperature stability, and improved the immune response upon immunization of animals. Specifically, the disclosed RBD designs can be produced approximately 7 times more efficiently than the native sequence, facilitating vaccine manufacturing on a global scale.