A Nonadjuvanted Polypeptide Nanoparticle Vaccine Confers Long-Lasting Protection against Rodent Malaria

作者：Kaba Stephen A; Brando Clara; Guo Qin; Mittelholzer Christian; Raman Senthilkumar; Tropel David; Aebi Ueli; Burkhard Peter; Lanar David E^*

来源：The Journal of Immunology, 2009, 183(11): 7268-7277.

DOI：10.4049/jimmunol.0901957

We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)(2)D of the malaria parasite Plasmodium berghei circumsporozoite protein. Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long-lived, protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2(b), H-2(d), and H-2(k) alleles. Immunized mice produced a CD4(+) T cell-dependent, high-titer, long-lasting, high-avidity Ab response against the B cell epitope. Mice were protected against an initial challenge of parasites up to 6 mo after the last immunization or for up to 15 mo against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal-specific B cells. The Journal of Immunology, 2009,183: 7268-7277.

• 出版日期2009-12-1