COMPOSITIONS AND METHODS FOR MUCOSAL VACCINATION AGAINST SARS-COV-2
Disclosed are peptides comprising a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS-CoV-2 antigen; and a trimerization domain. Disclosed are peptide complexes comprising three peptides, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; SARS-CoV-2 antigen; and a trimerization domain. Disclosed are compositions comprising any of the disclosed peptides or peptide complexes. Disclosed are methods for eliciting a protective immune response against SARS-CoV-2 comprising administering to a subject an effective amount of one or more of the compositions disclosed herein. Disclosed are methods of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to a subject an effective amount of one or more of the compositions disclosed herein.
1 . A peptide comprising
a monomeric Fc fragment of an immunoglobulin recognized by a neonatal receptor (FcRn);
a SARS-CoV-2 antigen, wherein the SARS-CoV-2 antigen is from an Omicron or delta strain; and
a trimerization domain.
2 . The peptide of claim 1 , wherein the SARS-CoV-2 antigen is a SARS-CoV-2 spike (S) antigen.
3 . The peptide of claim 2 , wherein the SARS-CoV-2 S antigen is full length soluble SARS-CoV-2 S protein, the S1 subunit of the SARS-CoV-2 S protein, the S2 subunit of the SARS-CoV-2 S protein, or the receptor binding domain (RBD) of the S1 subunit of the SARS-CoV-2 S protein.
4 . (canceled)
5 . (canceled)
6 . (canceled)
7 . The peptide of claim 1 , wherein the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises a mutation in the cysteine residues responsible for dimer formation.
8 . The peptide of claim 7 , wherein the cysteine residues are at position 226 and 229 of human IgG1.
9 . The peptide of claim 7 , wherein the mutation is a cysteine to serine substitution.
10 . The peptide of claim 1 , wherein C1q motif has been mutated such that it renders the fragment non-lytic.
11 . The peptide of claim 1 , wherein the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises a CH2 domain and a CH3 domain, and/or wherein the monomeric Fc fragment of an immunoglobulin recognized by a FcRn is an Ig Fc fragment.
12 . The peptide of claim 11 , wherein the monomeric Fc fragment of an immunoglobulin recognized by a FcRn comprises one or more mutations in the CH2 domain, wherein the one or more mutations in the CH2 domain ablate C1q binding to the monomeric Fc fragment.
13 . (canceled)
14 . The peptide of claim 1 , wherein the trimerization domain is a T4 fibritin trimerization domain.
15 . The peptide of claim 14 , wherein the T4 fibritin trimerization domain is foldon.
16 . The peptide of claim 1 , wherein the monomeric Fc fragment is conjugated to the carboxy terminal end of the SARS-CoV-2 spike protein.
17 . The peptide of claim 1 further comprising one or more linkers.
18 . The peptide of claim 17 , wherein at least one of the one or more linkers is between the trimerization domain and the SARS-CoV-2 antigen, and/or between the monomeric Fc fragment and the trimerization domain.
19 . (canceled)
20 . (canceled)
21 . A peptide complex comprising three peptides, wherein each of the peptides is the peptide of claim 1 .
22 . (canceled)
23 . A composition comprising one or more of the peptides of claim 1 .
24 . (canceled)
25 . (canceled)
26 . (canceled)
27 . A method for eliciting a protective immune response against SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising one or more of the peptides of claim 1 , wherein the SARS-CoV-2 is an Omicron or delta strain.
28 . A method for eliciting a protective immune response against SARS-CoV-2 comprising administering to a subject an effective amount of a composition comprising a peptide complex, wherein the peptide complex comprises three peptides forming a trimer, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium, wherein the SARS-CoV-2 is an Omicron or delta strain, and wherein the SARS-CoV-2 antigen is from the Omicron or delta strain.
29 . (canceled)
30 . (canceled)
31 . (canceled)
32 . (canceled)
33 . (canceled)
34 . (canceled)
35 . A method of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to the subject an effective amount of a composition comprising one or more of the peptides of claim 1 , wherein the SARS-CoV-2 is an Omicron or delta strain.
36 . A method of treating a subject exposed to SARS-CoV-2 or at risk of being exposed to SARS-CoV-2 comprising administering to the subject an effective amount of a composition comprising a peptide complex, wherein the peptide complex comprises three peptides forming a trimer, wherein each of the three peptides comprises a monomeric Fc fragment of an immunoglobulin recognized by a FcRn; a SARS-CoV-2 antigen; and a trimerization domain, wherein the administering is to a mucosal epithelium, wherein the SARS-CoV-2 is an Omicron or delta strain, and wherein the SARS-CoV-2 antigen is from the Omicron or delta strain.
37 . (canceled)
38 . (canceled)
39 . (canceled)