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 VEE3000 / 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.