Long-lasting humoral and cellular immune responses elicited by immunization with recombinant chimeras of the Plasmodium vivax circumsporozoite protein

Almeida, Ana Paula Morais Martins; Dias, Magno; Vieira, Carolina de Almeida Fagundes; Chávez-Olórtegui, Carlos; Gazzineli, Ricardo Tostes; Rodrigues, Maurício M.; Fujiwara, Ricardo Toshio; Bruna-Romero, Oscar

doi:10.1016/j.vaccine.2014.02.053

Cited by 11 publications

(17 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These malarial models suggest that the efficiency of parasite control requires both a humoral and a cellular immune response, most likely in cooperation, although the importance of each is not entirely clear. For example, immunity to the sporozoite depends on antibodies to surface proteins, such as CSP-2 [32, 33] and liver-stage antigen (LSA-1) [34]; these antigens induce the production of antibodies that neutralize or block the invasion of hepatocytes [35]. Once sporozoites have entered the hepatocyte, the parasite clearance in mice requires CD8 + T cells [36], natural killer cells (NK), and NKT and γ δ T cells that produce IFN- γ to eliminate infected hepatocytes [35].…”

Section: Plasmodiummentioning

confidence: 99%

Helminth Parasites Alter Protection againstPlasmodiumInfection

Salazar-Castañón

Legorreta-Herrera

Rodrı́guez-Sosa

2014

BioMed Research International

View full text Add to dashboard Cite

More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

show abstract

Section: Plasmodiummentioning

confidence: 99%

Helminth Parasites Alter Protection againstPlasmodiumInfection

Salazar-Castañón

Legorreta-Herrera

Rodrı́guez-Sosa

2014

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…RTS,S/AS01 has undergone extensive clinical testing and has been shown to induce significant protective immunity against P. falciparum in phase III trials5. The homologous CSP protein of P. vivax (PvCSP) is also actively being investigated as a component of a pre-erythrocytic vaccine against P. vivax , with particular emphasis on a vaccine that includes the PvCSP VK210 and VK247 central repeats to protect against the major strains of P. vivax circulating worldwide678910.…”

mentioning

confidence: 99%

“…The evaluation of the protective efficacy of P. falciparum vaccine candidates and vaccine formulations has greatly benefited from immunization-challenges studies performed in clinical trials using wild-type parasites in controlled human malaria infection (CHMI) studies6911121314. A similar direct evaluation of vaccines and protective immunity against P. vivax in CHMI studies has recently been reported7.…”

mentioning

confidence: 99%

Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

Salman

Montoya-Diaz

West

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation.

show abstract

“…ELISPOT assays revealed that PvRMC-CSP induced high frequencies of IFN-␥-secreting cells (more than 300 IFN-␥-secreting SFC/10 6 splenocytes) in all strains of mice tested. These responses are higher than those reported for the rPvCSP-ME vaccine candidate that induced more than 50 IFN-␥-secreting SFC/10 6 splenocytes in a single strain of mice (BALB/c) (63). The high IFN-␥/IL-4 ratios obtained after ex vivo stimulation with PvRMC-CSP allow us to infer that PvRMC-CSP elicits a Th1-biased immune response.…”

Section: Discussionmentioning

confidence: 64%

Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

et al. 2015

View full text Add to dashboard Cite

dPlasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside subSaharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimeric Plasmodium yoelii proteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimeric protein based on the P. vivax CSP (PvCSP). In this engineered protein, regions of the PvCSP predicted to contain human T cell epitopes were genetically fused to an immunodominant B cell epitope derived from the N-terminal region I and to repeat sequences representing the two types of PvCSP repeats. The chimeric protein was expressed in soluble form with high yield. As the immune response to PvCSP has been reported to be genetically restricted in the murine model, we tested the immunogenicity of PvRMC-CSP in groups of six inbred strains of mice. PvRMC-CSP was able to induce robust antibody responses in all the mouse strains tested. Synthetic peptides representing the allelic forms of the P. vivax CSP were also recognized to a similar extent regardless of the mouse strain. Furthermore, the immunization regimen induced high frequencies of multifunctional CD4؉ and CD8 ؉ PvRMC-CSP-specific T cells. The depth and breadth of the immune responses elicited suggest that immunization with PvRMC-CSP can circumvent the genetic restriction of the immune response to P. vivax CSP. Interestingly, PvRMC-CSP was also recognized by naturally acquired antibodies from individuals living in areas where malaria is endemic. These features make PvRMC-CSP a promising vaccine candidate for further development. P lasmodium vivax is the most widespread species of Plasmodium, causing up to 50% of the malaria cases occurring outside sub-Saharan Africa, with an estimated 2.48 billion people living in areas with risk of malaria transmission (1-4). Unlike Plasmodium falciparum, P. vivax is able to persist in a latent stage called hypnozoite within infected parenchymal liver cells. Activation of hypnozoites weeks or months after the primary infection leads to new blood stage infections, causing relapses and opportunities for further transmission (5).A vaccine targeting the P. vivax preerythrocytic stages preventing the entry of sporozoites into hepatocytes or inhibiting the liver stage development could block the production of hypnozoites. The most-characterized antigen and one of the few vaccine candidates for P. vivax tested in clinical trials is the circumsporozoite protein (CSP). CSP is an attractive target, since anti-CSP antibodies derived from naturally infected patients or from volunteers exposed to irradiated sporozoites have the ability to inhibit the infection of hepatic cells by sporozoites in vitro (6). Unlike P. ...

show abstract

Long-lasting humoral and cellular immune responses elicited by immunization with recombinant chimeras of the Plasmodium vivax circumsporozoite protein

Cited by 11 publications

References 46 publications

Helminth Parasites Alter Protection againstPlasmodiumInfection

Helminth Parasites Alter Protection againstPlasmodiumInfection

Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

Contact Info

Product

Resources

About