USA As Represented by Secretary of the Navy

Thomas L Richie

Martha Sedegah

Keith Limbach

Sofia A Casares

Teodor D Brumeanu

Joseph T Bruder

C Richter King

Denise Louise Doolan

Joao Aguiar

The present invention relates to recombinant chimeric molecules that are capable of providing T cell receptor (TCR) interaction and costimulation for activation and differentiation of pathogen-specific T cells toward effector T helper 1 (Th1) or T helper 2 (Th2) cells. The chimera may capable of elicit antibodies against pathogen-specific B cell epitope(s). The present invention also relates method of using these chimeric molecules in whole or as a component of a vaccine.

TH1/TH2 polarizing vaccines

The invention provides novel malaria polypeptides expressed at the pre-erythrocytic stage of the malaria life-cycle. The antigens can be utilized to induce an immune response against malaria in a mammal by administering the antigens in vaccine formulations or expressing the antigens in DNA or other nucleic acid expression systems delivered as a vaccine formulation.

[object Object]

The invention relates to a recombinant polypeptide construct comprising epitopes fromprotein circumsporozoite protein (CSP). The epitopes contain HLA class I binding motifs and stimulate an anti-malaria CD8T-cell response. The polypeptides can be incorporated into immunogenic formulations against malaria. Additionally, the antigens are useful for facilitating evaluation of immunogenicity of candidate malaria vaccines.

Provided is a transgenic animal model for testing immunogenicity and protective efficacy of human vaccines and the method for generating such a multitransgenic animal. Also disclosed are methods for screening compositions for human vaccine development. More specifically, a mouse model capable of expressing human leukocyte antigen DR4, and human costimulatory molecules (CD80) upon infusion of human HLA-matched hematopoietic stem cells, which can develop into a functional human immune system is provided.

Humanized transgenic mouse model

The invention provides a method of inducing an immune response against malaria in a mammal. The method comprises intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of (a) a first adenoviral vector comprising a nucleic acid sequence encoding acircumsporozoite protein (CSP) operably linked to a human CMV promoter, and/or (b) a second adenoviral vector comprising a nucleic acid sequence encoding aapical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter.

Growing community of inventors

Glenelg, MD, United States of America

Thomas L Richie