Broadly distributed T cell reactivity, with no immunodominant loci, to the pre-erythrocytic antigen thrombospondin-related adhesive protein ofPlasmodium falciparum in West Africans

Flanagan, Katie L.; Plebanski, Magdalena; Akinwunmi, Peter; Lee, Edwin A. M.; Reece, William H. H.; Robson, Kathryn; Hill, Adrian V. S.; Pinder, Margaret

doi:10.1002/(sici)1521-4141(199906)29:06<1943::aid-immu1943>3.0.co;2-1

Cited by 40 publications

(2 citation statements)

References 63 publications

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“…Peptides selected for testing are detailed in Table 1. They included peptides from the pre-erythrocytic antigens: circumsporozoite protein (CSP (Reece et al, 2004)), liver stage antigen-1 (LSA-1), thrombospodin-related adhesive protein (TRAP) (Flanagan et al, 1999), and the blood-stage antigens: apical membrane antigen-1 (AMA-1) (Lal et al, 1996; Udhayakumar et al, 2001), MB2 (pool of peptides MB1 (Nguyen & James, 2001) and MB2, (Nguyen & James, 2001)), and merozoite surface protein-1 (MSP-1, pool of peptides M1 (Parra et al, 2000) and M2, (Udhayakumar et al, 1995)). The peptides were synthesized and purified by high-performance liquid chromatography (HPLC) to >95% purity (Sigma Genosys, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Interferon-γresponses toPlasmodium falciparumvaccine candidate antigens decrease in the absence of malaria transmission

Ayieko

Ogola

Ochola

et al. 2017

PeerJ

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BackgroundMalaria elimination campaigns are planned or active in many countries. The effects of malaria elimination on immune responses such as antigen-specific IFN- γ responses are not well characterized.MethodsIFN- γ responses to the P. falciparum antigens circumsporozoite protein, liver stage antigen-1, thrombospondin-related adhesive protein, apical membrane antigen-1, MB2, and merozoite surface protein-1 were tested by ELISA in 243 individuals in highland Kenya in April 2008, October 2008, and April 2009, after a one-year period of interrupted malaria transmission from April 2007 to March 2008.ResultsWhile one individual (0.4%) tested positive for P. falciparum by PCR inOctober 2008 and another two (0.9%) tested positive in April 2009, no clinical malaria cases were detected during weekly visits. Levels of IFN-γ to all antigens decreased significantly from April 2008 to April 2009 (all P < 0.001).DiscussionNaturally acquired IFN- γ responses to P. falciparum antigensare short-lived in the absence of repeated P. falciparum infection. Even short periods of malaria interruption may significantly decrease IFN-γ responses to P. falciparum antigens.

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Section: Methodsmentioning

confidence: 99%

Interferon-γresponses toPlasmodium falciparumvaccine candidate antigens decrease in the absence of malaria transmission

Ayieko

Ogola

Ochola

et al. 2017

PeerJ

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“…Deregulation of this equilibrium can contribute to the generation of autoantibodies [149]. Persistent infections, such as malaria, can promote the generation of antibodies recognizing endogenous epitopes [150]. These medium-or low-affinity antibodies are polyreactive, recognizing Pf and human antigens simultaneously [151].…”

Section: Follicular Regulatory T Cells and Follicular Helper T Cellsmentioning

confidence: 99%

Immunosuppression in Malaria: Do Plasmodium falciparum Parasites Hijack the Host?

Calle

Mordmüller

Singh³

2021

Pathogens

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Malaria reflects not only a state of immune activation, but also a state of general immune defect or immunosuppression, of complex etiology that can last longer than the actual episode. Inhabitants of malaria-endemic regions with lifelong exposure to the parasite show an exhausted or immune regulatory profile compared to non- or minimally exposed subjects. Several studies and experiments to identify and characterize the cause of this malaria-related immunosuppression have shown that malaria suppresses humoral and cellular responses to both homologous (Plasmodium) and heterologous antigens (e.g., vaccines). However, neither the underlying mechanisms nor the relative involvement of different types of immune cells in immunosuppression during malaria is well understood. Moreover, the implication of the parasite during the different stages of the modulation of immunity has not been addressed in detail. There is growing evidence of a role of immune regulators and cellular components in malaria that may lead to immunosuppression that needs further research. In this review, we summarize the current evidence on how malaria parasites may directly and indirectly induce immunosuppression and investigate the potential role of specific cell types, effector molecules and other immunoregulatory factors.

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Long synthetic peptides encompassing thePlasmodium falciparum LSA3 are the target of human B and T cells and are potent inducers of B helper, T helper and cytolytic T cell responses in mice

et al. 2001

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We synthesized 17 long synthetic peptides (LSP) spanning the whole 200‐kDa Plasmodium falciparum liver stage antigen‐3 (LSA3), an antigen that induces protection in chimpanzee, and analyzed their immunogenicity in BALB/c mice and their antigenicity in individuals living in a hyper‐endemic malaria area. Our findings show that both specific antibodies and T cell proliferation against most LSA3‐LSP develop in malaria‐exposed adults. All individuals studied had detectable antibodies against a minimum of 6 and a maximum of 15 polypeptides. It is noteworthy that antibody prevalence and titers were as high against non‐repeat as repeat regions. Although the extent of T cell reactivity was lower than that observed for B cells, most of the sequences contained at least one T helper epitope, indicating that the majority of LSA3‐LSP contain both B and T cell epitopes within the same sequence. Injection of LSA3‐LSP with SBSA2 adjuvant in mice, showed strong immunogenicity for most of them, eliciting both T cell responses and specific antibody production. While all the peptides were immunogenic for B cells, different patterns of T cell responses were induced. These peptides were thus classified in three sets according to the levels of the T cell proliferative and of the IFN‐γ‐specific responses. Importantly, antibodies and T cells against some of the LSP were able to recognize LSA3 native protein on P. falciparum sporozoites. Additionally, some LSP (44–119, 1026–1095, 1601–1712) also contained epitopes recognized by H‐2d class I‐restricted T cells. These results led to the identification of numerous domains that are highly antigenic and immunogenic within the LSA3 protein, and underline the value of the LSP approach for vaccine development.

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Broadly distributed T cell reactivity, with no immunodominant loci, to the pre-erythrocytic antigen thrombospondin-related adhesive protein ofPlasmodium falciparum in West Africans

Cited by 40 publications

References 63 publications

Interferon-γresponses toPlasmodium falciparumvaccine candidate antigens decrease in the absence of malaria transmission

Interferon-γresponses toPlasmodium falciparumvaccine candidate antigens decrease in the absence of malaria transmission

Immunosuppression in Malaria: Do Plasmodium falciparum Parasites Hijack the Host?

Long synthetic peptides encompassing thePlasmodium falciparum LSA3 are the target of human B and T cells and are potent inducers of B helper, T helper and cytolytic T cell responses in mice

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