title: Safety, tolerability and immunogenicity of new formulations of the Plasmodium falciparum malaria peptide vaccine SPf66 combined with the immunological adjuvant QS-21.
abstract: SPf66 is a synthetic malaria peptide vaccine, which has been widely tested in combination with aluminium hydroxide (alum) as the adjuvant. Since this formulation is weakly immunogenic, we sought to improve its immunogenicity by using the saponin adjuvant QS-21. SPf66/QS-21 vaccines were evaluated for safety, tolerability and immunogenicity in healthy adults. The vaccines were found to be safe in 87/89 (97.8%) volunteers studied. However, two individuals developed severe vaccine allergy following the third dose of 1/3 SPf66/QS-21 formulations tested. Vaccine formulations containing QS-21 induced a 45- to over 200-fold increase in anti-SPf66 IgG titres over the alum formulation after the second and third doses, respectively. Anti-SPf66 antibody from some subjects reacted against asexual blood stage parasites, as demonstrated by immunofluorescence and immunoblotting. Antibody responses generated by the QS-21 formulations were of longer duration compared to those evoked by the alum formulation. While SPf66/alum has been found to induce only CD4+ T cell response, the QS-21 formulations exhibited the potential to also elicit SPf66-specific CD8+ responses. These observations demonstrate that the use of QS-21 can substantially enhance the immunogenicity of peptide vaccines, such as SPf66.
authors: Aquila Biopharmaceuticals Inc., Framingham, MA 01702, USA.
authors: Oscar
authors: O
authors: Kashala
authors: Roberto
authors: R
authors: Amador
authors: Maria V
authors: MV
authors: Valero
authors: Alberto
authors: A
authors: Moreno
authors: Arnoldo
authors: A
authors: Barbosa
authors: Beatrice
authors: B
authors: Nickel
authors: Claudia A
authors: CA
authors: Daubenberger
authors: Fanny
authors: F
authors: Guzman
authors: Gerd
authors: G
authors: Pluschke
authors: Manuel E
authors: ME
authors: Patarroyo
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003257:Consumer Product Safety; D004311:Double-Blind Method; D004361:Drug Tolerance; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000009:adverse effects / Q000276:immunology*; D011994:Recombinant Proteins; D012503:Saponins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C066269:SPf66 protein, Plasmodium; D012503:Saponins; D014614:Vaccines, Synthetic; C078785:saponin QA-21V1