Immune responses to multiple antigen peptides containing T and B epitopes from Plasmodium falciparum circumsporozoite protein of Brazilian individuals naturally exposed to malaria

Abstract

We have evaluated the immune responses of individuals living in a malaria endemic area of Brazil to the (T1B)4, a multiple antigen peptide (MAP) from Plasmodium falciparum circumsporozoite (CS) protein and the related monoepitope MAPs, B4 and (T1)4, and the linear peptides, T1B and B. The highest antibody frequencies were against MAPs containing the B cell epitope sequence (T1B)4 (42.2%) and B4 (28.8%), while the highest lymphoproliferative response frequencies were against the MAPs containing the T cell epitope sequence (T1)4 (47%) and (T1B)4 (36.4%). We analysed individual responses considering lymphoproliferative response to (T1)4 MAP and IgG antibody titre to (T1B)4 as patterns of ideal cellular and humoral responses, respectively. The frequency of responders, cellular and/or humoral was 66.6%, significantly higher than non responders (P = 0.003). We also determined the HLA class II haplotype of each individual but no association between these and immune response patterns to the MAPs was observed. The results showed that individuals primed against P. falciparum in their natural habitat, present a very diverse array of responses against the same peptide antigens, varying from no response in one-third of the individuals to cognate B and T cell responses. Our study underlines the importance of previous studies of vaccine candidates to guarantee that the immunization will be capable of reverting inefficient or absent responses to malaria epitopes.

Reactivity and Isotype Profiling of Monoclonal Antibodies using Multiple Antigenic Peptides

“…MAP A5 (DSLPHPQQATDDSGHB) also possessed proline residues. Overall, our data is consistent with other investigations (4,5) that confirm MAPs as effective peptides for evoking B-cell responses presumably by providing a stable immunogenic structure with a high ratio of peptide to lysine core. Recent studies investigating both T-and B-cell responses to MAPs highlight a branched configuration as more efficient at eliciting antibodies in vivo.…”

“…However, there remains a concern of whether MAPs carrying potential B-cell epitopes alone generate suitable monoclonal reagents with appropriate reactivity and immunoglobulin isotype for desired applications. (5) Monoclonal antibodies (MAbs) serve as diagnostic and therapeutic reagents as well as molecular probes to identify macromolecules and cells. (6) Their wide application stems from an ability to produce an inexhaustible supply of antibody that is monospecific and of reproducible quality.…”

Development of Peptide Mimotopes of Lipooligosaccharide from NontypeableHaemophilus influenzaeas Vaccine Candidates

“…To produce an experimental vaccine candidate for human use, these promising peptides need to be conjugated to clinically acceptable carriers, such as TT, and conventionally tested in animal models, such as in active protection models of mouse pulmonary clearance and chinchilla OM by systemic or mucosal administration. Meanwhile, these peptides can be rationally designed with multivalent LOS mimotopes, multiple Ag peptides, or to contain additional structures, including Th cell epitopes and built-in adjuvants (53)(54)(55)(56). These applications might further improve immunogenicity of these LOS mimotopes in vivo.…”

Peptide dendrimers

“…Avila et al [132] An effective malaria vaccine should contain a parasite-derived epitope to elicit CD4 + T cells that could function as a source of both inhibitory lymphokines and T-helper factors for antibody responses. The authors [133] used a series of CD4 + T-cell clones, derived from a volunteer immunized by irradiated P. falciparum sporozoites, to identify a class II restricted T-helper epitope, designated T1, in the 5 repeat region of the CSP.…”