ArticlePloS one2014
IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 68 citations in OpenAlex.
- Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and Associated With Protection in a Phase 1/2a Trial.The Journal of infectious diseases · 2021Trial
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- Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis.Scientific reports · 2017Trial
- Comparison of major, minor and junctional circumsporozoite protein epitopes for malaria vaccine design.NPJ vaccines · 2025Article
- Targeting T-Cell Activation for Malaria Immunotherapy: Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Exploring malaria parasite surface proteins to devise highly immunogenic multi-epitope subunit vaccine for Plasmodium falciparum.Journal, genetic engineering & biotechnology · 2024Article
- Biophysical characterization of the Plasmodium falciparum circumsporozoite protein's N-terminal domain.Protein science : a publication of the Protein Society · 2024Article
- Poly I:C elicits broader and stronger humoral and cellular responses to aFrontiers in immunology · 2024Article
- Choice of adjuvant and antigen composition alters the immunogenic profile of a SARS-CoV-2 subunit vaccine.Frontiers in drug delivery · 2024Article
- Optimizing immunogenicity and product presentation of a SARS-CoV-2 subunit vaccine composition: effects of delivery route, heterologous regimens with self-amplifying RNA vaccines, and lyophilization.Frontiers in immunology · 2024Article
- A candidate antibody drug for prevention of malaria.Nature medicine · 2024Article
- Protective antibody threshold of RTS,S/AS01 malaria vaccine correlates antigen and adjuvant dose in mouse model.NPJ vaccines · 2023Article
- Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection.Nature communications · 2023Article
- Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9.Nature communications · 2023Article
- A tool for evaluating heterogeneity in avidity of polyclonal antibodies.Frontiers in immunology · 2023Article
- Novel antibody competition binding assay identifies distinct serological profiles associated with protection.Frontiers in immunology · 2023Article
- Article
- Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720.Frontiers in immunology · 2022Article
- Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection.NPJ vaccines · 2021Article
- Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice.NPJ vaccines · 2021Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1)/T(H2) response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans.
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