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Updated: Jun 21, 2026
High Yield Purification of Plasmodium falciparum Merozoites For Use in Opsonizing Antibody Assays
Published on: July 17, 2014
Probing novel epitopes on the Plasmodium falciparum circumsporozoite protein for vaccine development
Pascal S Krenger1,2,3, Magali Roques4, Anne-Cathrine S Vogt5,6,7
1Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland. pascal.krenger@unibe.ch.
Insights
New malaria vaccines targeting the NANP repeat region of Plasmodium falciparum circumsporozoite protein (PfCSP) show promising immunogenicity and efficacy in mice. These novel candidates induce protective antibodies and confer sterile protection without adjuvants.
Area of Science:
- Malariology and Vaccinology
- Protein Engineering and Immunology
Background:
- The World Health Organization recommends RTS,S and R21 vaccines against Plasmodium falciparum (Pf) malaria, both targeting the Pf circumsporozoite protein (PfCSP).
- Optimal neutralization of Pf sporozoites requires antibodies binding to both NANP repeats and the NPDP junction domain of PfCSP, a target not included in current vaccines.
Purpose of the Study:
- To evaluate novel malaria vaccine candidates targeting different regions of PfCSP, including the NANP repeat and NPDP junction domains.
- To assess the immunogenicity and protective efficacy of these candidates in a mouse model.
Main Methods:
- Development of vaccine candidates using cucumber mosaic virus-like particles (CuMVTT-VLPs) displaying various PfCSP repeat sequences (NANP, NPDP, NVDP).
- Immunization of BALB/c mice and assessment of humoral responses (IgM/IgG).
- Efficacy studies using chimeric Plasmodium berghei expressing PfCSP (Pb/PfCSP) sporozoites to challenge immunized mice.
Main Results:
- A positive correlation was observed between the number of targeted NANP repeats and the induction of specific IgM/IgG antibodies.
- Vaccine candidates targeting NANP repeats demonstrated enhanced protection against parasitemia, with high-avidity/affinity antibody formation being NANP repeat-dependent.
- Targeting other PfCSP sites, including the NPDP junction domain, did not enhance vaccine efficacy compared to NANP repeat-focused candidates.
Conclusions:
- The NANP repeat region of PfCSP plays a dominant role in inducing protective antibodies against malaria.
- Novel CuMVTT-VLP-based malaria vaccine candidates targeting NANP repeats exhibit excellent immunogenicity.
- These new vaccine candidates confer sterile protection in mice, highlighting their potential even without adjuvants.
Abstract:
RTS,S and R21 are the only vaccines recommended by the WHO to protect children from Plasmodium falciparum (Pf) clinical malaria. Both vaccines target the Pf sporozoite surface protein circumsporozoite protein (CSP). Recent studies showed that human antibodies neutralize Pf sporozoites most efficiently when simultaneously binding to the PfCSP NANP repeat and the NPDP junction domain. However, neither RTS,S nor R21 targets this junction domain. To test the potential of the NPDP junction domain and other sites of PfCSP as innovative vaccine targets, we developed multiple vaccine candidates based on cucumber mosaic virus-like particles (CuMVTT-VLPs). These candidates vary in several aspects: the number of targeted NANP repeats, the presence or absence of the junction domain, the cleavage site, and up to three NVDP repeats within the target sequence. Immunogenicity and efficacy studies were conducted in BALB/c mice, utilizing chimeric Plasmodium berghei (Pb) sporozoites, in which the endogenous CSP has been replaced by PfCSP (Pb/PfCSP). We observed a positive association between the number of targeted NANP repeats and the induction of specific IgM/IgG antibodies. Elevated humoral responses led to enhanced protection against parasitemia after Pb/PfCSP sporozoite challenge. Especially high-avidity/affinity antibody formation and vaccine protection were NANP repeat-dependent. Intriguingly, vaccine efficacy was not enhanced by targeting sites on PfCSP other than the NANP repeats. Our data emphasize the dominant role of the NANP repeat region for induction of protective antibodies. Furthermore, we present here novel malaria vaccine candidates with an excellent immunogenic profile that confer sterile protection in mice, even in absence of adjuvants.
