Nant COVID vaccine cross reactivity
Recombinant SARS-CoV2 vaccine compositions and methods are presented that have unexpected cross-reactivity against a variety of other coronaviruses, and particularly against SARS-CoV1, MERS-CoV, OC43-CoV, and HKU1-CoV in addition to significant reactivity against SARS-CoV2A. Moreover, the vaccine compositions presented herein also produced cross-reactive memory B cells as well as cross-reactive memory T cells with cross-reactivity spanning a relatively wide range of different coronaviruses.
1. A method of eliciting in a subject an immune response against a coronavirus, the method comprising:
administering to the subject a recombinant vaccine composition in a prime and/or boost administration,
wherein the recombinant vaccine composition has a first portion encoding a severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein (N) that is fused to an endosomal targeting sequence (N-ETSD), wherein the first portion comprises a nucleic acid encoding the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7,
wherein the first portion is functionally coupled to one or more regulatory elements that enable N-ETSD expression; and a second portion encoding a SARS virus spike protein (S),
wherein the second portion is functionally coupled to one or more regulatory elements that enable S expression;
wherein the vaccine composition is administered in an amount that elicits the immune response; and
wherein the immune response extends from SARS-Co V2 to a Wuhan, Alpha, Epsilon, Gamma, or Beta variant of SARS-CoV2.
2. The method of claim 1 , wherein the immune response comprises the generation of antibodies that bind to at least two of the Wuhan, Alpha, Epsilon, Gamma, and Beta variants of SARS-CoV2.
3. The method of claim 1 , wherein the immune response is generation of cytotoxic T cells that have cytotoxicity against different cells harboring Wuhan, Alpha, Epsilon, Gamma, or Beta variants of SARS-CoV2.
4. The method of claim 1 , wherein the immune response is generation of memory T cells and/or memory B cells.
5. The method of claim 1 , wherein the N is from SARS-CoV-2.
6. The method of claim 1 , wherein the endosomal targeting sequence of the N-ETSD is encoded at a 5′-end of the first portion and/or wherein the endosomal targeting sequence of the N-ETSD is encoded at a 3′-end of the first portion.
7. The method of claim 1 , wherein the first and second portions are arranged in a bicistronic sequence.
8. The method of claim 1 , wherein the first portion has nucleotide sequence SEQ ID NO:2.
9. The method of claim 1 , wherein the S protein has the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:4.
10. The method of claim 1 , wherein the second portion has nucleotide sequence SEQ ID NO:5 or SEQ ID NO:6.
11. The method of claim 1 , wherein the recombinant vaccine composition is formulated as a recombinant virus.
12. The method of claim 11 , wherein the recombinant virus is an adenovirus having an E1 gene region deletion and an E2b gene region deletion.
13. The method of claim 1 , wherein the recombinant vaccine composition is formulated as a recombinant RNA.
14. The method of claim 1 , wherein the recombinant vaccine composition is formulated as a recombinant DNA.
15. The method of claim 1 , wherein the recombinant vaccine composition is administered in the prime and the boost administration.
16. The method of claim 1 , wherein the recombinant vaccine composition is administered only in the boost administration.
17. A method of generating memory B cells having specificity for the Wuhan, Alpha, Epsilon, Gamma, or Beta variant of SARS-CoV2, the method comprising:
administering to a subject a recombinant vaccine composition in a prime and/or boost administration,
wherein the recombinant vaccine composition has a first portion encoding a severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein (N) that is fused to an endosomal targeting sequence (N-ETSD), wherein the first portion comprises a nucleic acid encoding the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7,
wherein the first portion is functionally coupled to one or more regulatory elements that enable N-ETSD expression; and a second portion encoding a SARS virus spike protein (S),
wherein the second portion is functionally coupled to one or more regulatory elements that enable S expression; and
wherein the vaccine composition is administered in an amount that elicits generation of the memory B cells.
18. A method of generating memory T cells having specificity for the Wuhan, Alpha, Epsilon, Gamma, or Beta variant of SARS-CoV2, the method comprising:
administering to a subject a recombinant vaccine composition in a prime and/or boost administration,
wherein the recombinant vaccine composition has a first portion encoding a severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein (N) that is fused to an endosomal targeting sequence (N-ETSD), wherein the first portion comprises a nucleic acid encoding the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7,
wherein the first portion is functionally coupled to one or more regulatory elements that enable N-ETSD expression; and a second portion encoding a SARS virus spike protein (S), wherein the second portion is functionally coupled to one or more regulatory elements that enable S expression; and
wherein the vaccine composition is administered in an amount that elicits generation of the memory T cells.