Polyepitope carrier protein
View Patent ↗The invention relates to polyepitope carrier proteins that comprise at least five CD4+T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are use useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines are particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.
1. A nucleic acid molecule which encodes a carrier protein comprising at least five different CD4+ T cell epitopes, wherein the CD4+ T cell epitopes are from tetanus toxin and from Plasmodium falciparum circumsporozite protein, hepatitis B surface antigen, hepatitis B nuclear core protein, influenza matrix protein, influenza haemagglutinin, diphtheria toxoid, diphtheria toxin mutant CRM 197, group B Neisseria meningitidis outer membrane protein complex, pertussis toxin or heat shock protein 70.
2. The nucleic acid molecule of claim 1 wherein said nucleic acid molecule is DNA.
3. A cloning or expression vector comprising the nucleic acid molecule according to claim 1 or claim 2 .
4. A host cell transformed or transfected with the vector of claim 3 .
5. A method of preparing a carroer protein comprising at least five different CD4+T cell epitopes, wherein the CD4+T cell epitopes are from tetanus toxin and from Plasmodium falciparum circumsporozite protein, hepatitis B surface antigen, hepatitis B nuclear core protein, influenza matrix protein, influenza haemagglutinin, diphtheria toxoid, diphtheria toxin mutant CRM 197, group B Neisseria meningitidis outer membrane protein complex, pertussis toxin or heat shock protein 70 comprising expressing the vector of claim 3 in a host cell and culturing said host cell under conditions wherein said carrier protein is expressed, and recovering said carrier protein thus expressed.
6. The method of claim 5 , wherein the host cell is an E. coli bacterium.
7. The nucleic acid molecule of claim 1 , wherein the CD4+epitopes are selected from P23TT, P32TT, P21TT, PFT3, P30TT, P2TT, HBVnc, influenza haemagglutinin (HA), HbsAg, influenza matrix (MT) and hsp70 CD4+T cell epitopes.
8. The nucleic acid molecule of claim 1 , wherein the carrier protein comprises P23TT, P32TT, P21TT, PFT3, P30TT, P2TT, HBVnc, influenza haemagglutinin (HA), HbsAg, and influenza matrix (MT) CD4+T cell epitopes.
9. The nucleic acid molecule of claim 1 , wherein the carrier protein comprises P23TT, P32TT, P21TT, PFT3, P30TT, P2TT, HBVnc, influenza haemagglutinin (HA), HbsAg, influenza matrix (MT) and hsp70CD4+T cell epitopes.
10. The nucleic acid molecule of claim 1 , wherein the carrier protein comprises P23TT, P32TT, P21TT, PFT3, P30TT, and P2TT CD4+T cell epitopes.
11. The nucleic acid molecule of claim 1 , wherein the CD4+epitopes are human CD4+T cell epitopes.
12. The nucleic acid molecule of claim 1 , wherein the carrier protein encoded comprises one or more of the N6, N10 or N19 proteins.