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

Abstract

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)2D of the malaria parasite Plasmodium berghei circumsporozoite protein (CSP). 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-2b, H-2d and H-2k alleles. Immunized mice produced a CD4+ T cell dependent, high titer, long lasting, high avidity antibody response against the B cell epitope. Mice were protected against an initial challenge of parasites given up to 6 months after the last immunization or for up to 15 months 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.

Expression of peptide nanoparticles containing a porcine reproductive and respiratory syndrome (PRRS) virus epitope in plants

“…As shown in Figure 1, we were able to obtain particles in both cases with sizes between 16-25 nm. The size and morphology of the nanoparticles closely resembled those obtained in bacteria (Babapoor et al, 2011;Kaba et al, 2009;Pimentel et al, 2009). This data demonstrated that nanoparticles were successfully Uribe-Campero et al 1603 formed in the plant cytoplasm.…”

“…A nanoparticle with this type of architecture can be used as a vaccine by extending the ends of the monomer with an epitope sequence (Babapoor et al, 2011). Nanoparticles of this type have only been expressed in bacterial systems and employed to express epitopes of Plasmodium berghei (Kaba et al, 2009), avian influenza (Babapoor et al, 2011) and severe acute respiratory syndrome virus (Pimentel et al, 2009).…”

Molecular vaccines for malaria

“…4). 208 Furthermore, a SAPN displaying the P. falciparum CSP repeat epitope completely protected mice from challenge using a P. falciparum CSP transgenic P. berghei parasite without the requirement for additional adjuvant (D. Lanar, personal communication).…”

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

“…We have extensively used exogenous lipids and polymers to form self-adjuvanting delivery systems that obviate the use of toxic adjuvants [8][9][10][11][12][13]. Recently, it has been reported that self-assembled peptides exclusively composed of endogenous amino acids were able to stimulate immune responses [14][15][16].…”