Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

Described herein are processes for purifying infectious virus particles and uses of protamine in such processes.

Described herein are improved purification methods for virus vaccines and compositions. Also described are Zika, Chikungunya, dengue and yellow fever vaccines and methods of producing and administering said vaccines to subjects in need thereof.

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

Embodiments herein relate to compositions of and methods for live viruses. In certain embodiments, a live, attenuated virus composition includes, but is not limited to, one or more live, attenuated viruses and compositions to reduce inactivation and/or degradation of the live, attenuated virus. In other embodiments, the live, attenuated virus composition may be a vaccine composition. In yet other compositions, a live, attenuated virus composition may include at least one carbohydrate, at least one protein and at least one high molecular weight surfactants for reducing inactivation and/or degradation of the live, attenuated virus.

A novel and improved vaccine for prevention of disease caused by the Severe Acute Respiratory Syndrome-2 (SARS-2), /COVID-19 virus. Current mRNA and Adenovirus vaccine technologies for SARS-2 provide high levels of serum Immunoglobin G (IgG), antibodies against the original Wuhan strain, but there are now hundreds of mutant strains which can evade both vaccine and convalescent antibodies. These vaccines also do not provide strong mucosal IgA class antibodies which provide wider protection against mutant strains of Flu A and other respiratory viruses. The ability of these technologies to provide high levels of protection is in question, as serum neutralizing antibodies may decline to undetectable levels after six months. The appearance of mutant strains such as the Beta, Gamma, Delta, and Epsilon strains, containing altered amino acid sequences capable of evading vaccine-induced antibodies, calls for new vaccine technologies that can be quickly altered to meet this threat. The following describes a combination approach to prevention of infection by SARS-2/COVID-19. This combination consists of a priming injection of Recombinant Replicative Particles (VRP) derived from the Alphavirus Venezuelan Equine Encephalitis (VEE) strain 3000/3526, with insertion of a Delta/B.1.617.2 SARS-2/COVID-19 spike 1 glycoprotein (gp)-Receptor-Binding Domain (RBD) gene. The insertion of Internal Ribosome Entry Sites (IRES), elements between the 26S promoter and the SARS-2/COVID RBD gene allows for more efficient translation of the SARS-2/COVID gene products. The VEE.sup.3000/3256 VRP are produced from plasmids, so while they are infectious for one replicative cycle in vivo, progeny VRP are replication incompetent. The priming is followed by one or more intranasal administrations of a suspension of recombinant SARS-2/COVID-19 envelope spike 1 glycoproteins (gp), from selected mutant strains, combined with the pulmonary surfactant adjuvant, SF-10. The goal of the invention is to safely provide multiple immune layers of protection in both the upper and lower respiratory tracts, with induction of both mucosal IgA and serum IgG antibodies, as well as effector Cytotoxic T Lymphocyte (CTL), cells recognizing conserved regions of the SARS-2/COVID-19 virus genome. Secondary goals are to reduce the risk of antibody-dependent enhancement (ADE), of infection, a major concern with other SARS-2/COVID-19 vaccine designs, and to provide capacity to protect against mutant emergent strains of SARS-2/COVID-19 with annual intranasal boosters of new spike glycoproteins.

Described herein are improved purification methods for Zika virus vaccines and compositions. Also described are Zika vaccines and methods of producing and administering said Zika vaccines to subjects in need thereof.

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

The present disclosure includes, among other things, non-natural nucleotides useful as 5′ caps for RNA nucleotides. The present disclosure also includes, among other things, compositions and methods using delivery and vaccine RNA nucleotide compositions that include non-natural nucleotides as 5′ caps.

Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.