The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.

The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.

Disclosed are an attenuation system and the use thereof for attenuating plasmodia, specifically the use of an EF1g gene for attenuating plasmodia. The attenuation system regulates the expression or degradation of the EF1g gene by using a regulatory system, thereby controlling the growth of plasmodia and achieving the attenuation of plasmodia.

Disclosed are an attenuation system and the use thereof for attenuating plasmodia, specifically the use of an EF1g gene for attenuating plasmodia. The attenuation system regulates the expression or degradation of the EF1g gene by using a regulatory system, thereby controlling the growth of plasmodia and achieving the attenuation of plasmodia.

Formulations and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed. The formulations generally comprise a TLR4 agonist and a metabolizable oil at a concentration of about 0.01%-1% v/v, wherein the hydrophobic:lipophilic balance (HLB) of the emulsion is greater than about 9.

Formulations and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed. The formulations generally comprise a TLR4 agonist and a metabolizable oil at a concentration of about 0.01%-1% v/v, wherein the hydrophobic:lipophilic balance (HLB) of the emulsion is greater than about 9.

The invention relates to pharmaceutical compositions comprising at least one antigen and an adjuvant composition, where the adjuvant composition comprises a saponin and a liposome. The liposome of the composition comprises monophosphoryl lipid A (MPLA), cholesterol and a phospholipid that is in a liquid crystalline state at greater than or equal to 23° C., and the concentration of cholesterol to lipid in the liposome is greater than 50% (mol/mol). The antigen in the composition is a soluble Plasmodium falciparum recombinant circumsporozoite protein (rCSP) comprising the amino acid sequence of SEQ ID NO:1, or a P. falciparum rCSP peptide that is at least 95% identical to the amino acid sequence of SEQ ID NO:1.

The invention relates to pharmaceutical compositions comprising at least one antigen and an adjuvant composition, where the adjuvant composition comprises a saponin and a liposome. The liposome of the composition comprises monophosphoryl lipid A (MPLA), cholesterol and a phospholipid that is in a liquid crystalline state at greater than or equal to 23° C., and the concentration of cholesterol to lipid in the liposome is greater than 50% (mol/mol). The antigen in the composition is a soluble Plasmodium falciparum recombinant circumsporozoite protein (rCSP) comprising the amino acid sequence of SEQ ID NO:1, or a P. falciparum rCSP peptide that is at least 95% identical to the amino acid sequence of SEQ ID NO:1.

An immunogen useful for treating malaria generally includes an immunogenic carrier and an antigenic malaria circumsporozoite protein (CSP) peptide that includes the peptide NANPNVDPNANPNVD (SEQ ID NO:2) linked to the immunogenic carrier. The immunogen may be administered to a subject having or at risk of having malaria. Alternatively, the immunogen may be administered to an individual having or at risk of having Plasmodium falciparum blood stage parasitemia. In some cases, the immunogen can be administered in combination with another therapeutic agent for treating malaria of Plasmodium falciparum blood stage parasitemia.

An immunogen useful for treating malaria generally includes an immunogenic carrier and an antigenic malaria circumsporozoite protein (CSP) peptide that includes the peptide NANPNVDPNANPNVD (SEQ ID NO:2) linked to the immunogenic carrier. The immunogen may be administered to a subject having or at risk of having malaria. Alternatively, the immunogen may be administered to an individual having or at risk of having Plasmodium falciparum blood stage parasitemia. In some cases, the immunogen can be administered in combination with another therapeutic agent for treating malaria of Plasmodium falciparum blood stage parasitemia.