Recombinant HIV-1 envelope proteins comprising stabilizing two-cysteine mini-domains in gp41
The present invention provides a recombinant HIV Env antigenic protein, a virus-like particle and a recombinant HIV virus. The present invention further provides a vaccine comprising the recombinant HIV Env antigenic protein, the virus-like particle or recombinant HIV virus.
1. A recombinant HIV Env antigenic protein, comprising:
an extracellular domain with major antigenic epitopes;
a fusion peptide; and
a membrane proximity external region (MPER);
wherein at least one two-cysteine mini-domain selected from CxxC (SEQ ID NO 3), CxxxC (SEQ ID NO 4) or CxxxxC (SEQ ID NO 5) is present in the MPER, where x represents any amino acids as long as they do not break the helix structure.
2. A recombinant HIV Env antigenic protein comprising:
an extracellular domain with major antigenic epitopes;
a fusion peptide;
a membrane proximity external region (MPER);
a transmembrane domain (TMD); and
a cytoplasmic domain (CPD);
wherein the at least one two-cysteine mini-domain selected from CxxC (SEQ ID NO 3), CxxxC (SEQ ID NO 4) or CxxxxC (SEQ ID NO 5) is present in the MPER or TMD, where x represents any amino acids as long as they do not break the helix structure.
3. The recombinant HIV Env antigenic protein of claim 2 , wherein the TMD is from one authentic HIV Env protein and the TMD is modified to contain the at least one two-cysteine mini domain.
4. The recombinant HIV Env antigenic protein of claim 2 , wherein the TMD is an artificially synthetic peptide or derived from a non-Env protein forming trimers in its native configuration.
5. The recombinant HIV Env antigenic protein of claim 1 , wherein the recombinant HIV Env antigenic protein is encoded by a DNA sequence, and the DNA sequence is cloned into an in vivo expression vector.
6. The recombinant HIV Env antigenic protein of claim 2 , wherein recombinant HIV Env antigenic protein is encoded by a DNA sequence, and the DNA sequence is cloned into the an in vivo expression vector.
7. The recombinant HIV Env antigenic protein of claim 1 , wherein the recombinant HIV Env antigenic protein is used in an immunogenic composition against HIV infection.
8. The recombinant HIV Env antigenic protein of claim 2 , wherein the recombinant HIV Env antigenic protein is used in an immunogenic composition against HIV infection.
9. The recombinant HIV Env antigenic protein of claim 1 , wherein the recombinant HIV Env antigenic protein is incorporated into a virus-like particle.
10. The recombinant HIV Env antigenic protein of claim 2 , wherein the recombinant HIV Env antigenic protein is incorporated into a virus-like particle.
11. The recombinant HIV Env antigenic protein of claim 1 , wherein the recombinant HIV Env antigenic protein is incorporated into a recombinant HIV virus.
12. The recombinant HIV Env antigenic protein of claim 2 , wherein the recombinant HIV Env antigenic protein is incorporated into a recombinant HIV virus.