scholarly journals Potential and Limitations of Cross-Protective Vaccine against Malaria by Blood-Stage Naturally Attenuated Parasite

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 375
Author(s):  
Takashi Imai ◽  
Kazutomo Suzue ◽  
Ha Ngo-Thanh ◽  
Chikako Shimokawa ◽  
Hajime Hisaeda
Keyword(s):  
Malaria Vaccine ◽  
Vaccination Strategy ◽  
Plasmodium Yoelii ◽  
Blood Stage ◽  
Plasmodium Berghei Anka ◽  
Complete Protection ◽  
Vaccine Trials ◽  
Multiple Species ◽  
Stage Parasite ◽  
Blood Stage Parasite

Human malaria vaccine trials have revealed vaccine efficacy but improvement is still needed. In this study, we aimed to re-evaluate vaccination with blood-stage naturally attenuated parasites, as a whole-organism vaccine model against cross-strain and cross-species malaria, to establish a better vaccination strategy. C57BL/6 mice controlled blood-stage Plasmodium yoelii 17XNL (PyNL) within 1 month of infection, while mice with a variety of immunodeficiencies demonstrated different susceptibilities to PyNL, including succumbing to hyperparasitemia. However, after recovery, survivors had complete protection against a challenge with the lethal strain PyL. Unlike cross-strain protection, PyNL-recovered mice failed to induce sterile immunity against Plasmodium berghei ANKA, although prolonged survival was observed in some vaccinated mice. Splenomegaly is a typical characteristic of malaria; the splenic structure became reorganized to prioritize extra-medullary hematopoiesis and to eliminate parasites. We also found that the peritoneal lymph node was enlarged, containing activated/memory phenotype cells that did not confer protection against PyL challenge. Hemozoins remained in the spleen several months after PyNL infection. Generation of an attenuated human blood-stage parasite expressing proteins from multiple species of malaria would greatly improve anti-malaria vaccination.

scholarly journals Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

2010 ◽  
Vol 9 (1) ◽  
pp. 296 ◽  
Author(s):  
Cathrine Olesen ◽  
Karima Brahimi ◽  
Brian Vandahl ◽  
Susana Lousada-Dietrich ◽  
Prajakta S Jogdand ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Igg Subclasses ◽  
Blood Stage ◽  
Stage Parasite ◽  
Blood Stage Parasite

scholarly journals Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults

2019 ◽  
Vol 71 (6) ◽  
pp. 1481-1490
Author(s):  
Sara A Healy ◽  
Sean C Murphy ◽  
Jen C C Hume ◽  
Lisa Shelton ◽  
Steve Kuntz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Phase I ◽  
Malaria Infection ◽  
Blood Smear ◽  
Blood Stage ◽  
Controlled Human Malaria Infection ◽  
Smear Negative ◽  
Parasite Exposure ◽  
Stage Parasite ◽  
Blood Stage Parasite

Abstract Background Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against a homologous Plasmodium falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs, such as primaquine, act against liver-stage parasites. Here, we evaluated CVac regimens using primaquine and/or chloroquine as the partner drug to discern whether blood-stage parasite exposure impacts protection against homologous controlled human malaria infection. Methods In a Phase I, randomized, partial double-blind, placebo-controlled study of 36 malaria-naive adults, all CVac subjects received chloroquine prophylaxis and bites from 12–15 P. falciparum–infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received postexposure primaquine (CVac-primaquine/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After a chloroquine washout, subjects, including treatment-naive infectivity controls, underwent homologous, PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days. Results No serious adverse events occurred. During CVac, all but 1 subject in the study remained blood-smear negative, while only 1 subject (primaquine/chloroquine arm) remained polymerase chain reaction–negative. Upon challenge, compared to infectivity controls, 3/3 chloroquine arm subjects displayed delayed patent parasitemia (P = .01) but not sterile protection, while 3/11 primaquine/chloroquine subjects remained blood-smear negative. Conclusions CVac-primaquine/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine postexposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity. Clinical Trials Registration NCT01500980.

scholarly journals Identification of the asymptomatic Plasmodium falciparum and Plasmodium vivax gametocyte reservoir under different transmission intensities

2021 ◽  
Vol 15 (8) ◽  
pp. e0009672
Author(s):  
Cristian Koepfli ◽  
Wang Nguitragool ◽  
Anne Cristine Gomes de Almeida ◽  
Andrea Kuehn ◽  
Andreea Waltmann ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Light Microscopy ◽  
Papua New Guinea ◽  
Parasite Density ◽  
Solomon Islands ◽  
Age Groups ◽  
Blood Stage ◽  
Cross Sectional ◽  
Stage Parasite ◽  
Blood Stage Parasite

Background Understanding epidemiological variables affecting gametocyte carriage and density is essential to design interventions that most effectively reduce malaria human-to-mosquito transmission. Methodology/Principal findings Plasmodium falciparum and P. vivax parasites and gametocytes were quantified by qPCR and RT-qPCR assays using the same methodologies in 5 cross-sectional surveys involving 16,493 individuals in Brazil, Thailand, Papua New Guinea, and Solomon Islands. The proportion of infections with detectable gametocytes per survey ranged from 44–94% for P. falciparum and from 23–72% for P. vivax. Blood-stage parasite density was the most important predictor of the probability to detect gametocytes. In moderate transmission settings (prevalence by qPCR>5%), parasite density decreased with age and the majority of gametocyte carriers were children. In low transmission settings (prevalence<5%), >65% of gametocyte carriers were adults. Per survey, 37–100% of all individuals positive for gametocytes by RT-qPCR were positive by light microscopy for asexual stages or gametocytes (overall: P. falciparum 178/348, P. vivax 235/398). Conclusions/Significance Interventions to reduce human-to-mosquito malaria transmission in moderate-high endemicity settings will have the greatest impact when children are targeted. In contrast, all age groups need to be included in control activities in low endemicity settings to achieve elimination. Detection of infections by light microscopy is a valuable tool to identify asymptomatic blood stage infections that likely contribute most to ongoing transmission at the time of sampling.

scholarly journals Evidence for a Common Role for the Serine-Type Plasmodium falciparum Serine Repeat Antigen Proteases: Implications for Vaccine and Drug Design

2007 ◽  
Vol 75 (12) ◽  
pp. 5565-5574 ◽  
Author(s):  
Joanne E. McCoubrie ◽  
Susanne K. Miller ◽  
Tobias Sargeant ◽  
Robert T. Good ◽  
Anthony N. Hodder ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Functional Redundancy ◽  
Blood Stage ◽  
Parasite Development ◽  
Serine Residue ◽  
Human Malaria Parasite ◽  
Knock Out ◽  
Genetic Deletion ◽  
Stage Parasite ◽  
Blood Stage Parasite

ABSTRACT Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases of Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place of the canonical cysteine. The human malaria parasite Plasmodium falciparum possesses six “serine-type” (SERA1 to SERA5 and SERA9) and three “cysteine-type” (SERA6 to SERA8) SERAs. Here, we investigate the importance of the serine-type SERAs to blood-stage parasite development and examine the extent of functional redundancy among this group. We attempted to knock out the four P. falciparum serine-type SERA genes that have not been disrupted previously. SERA1, SERA4, and SERA9 knockout lines were generated, while only SERA5, the most strongly expressed member of the SERA family, remained refractory to genetic deletion. Interestingly, we discovered that while SERA4-null parasites completed the blood-stage cycle normally, they exhibited a twofold increase in the level of SERA5 mRNA. The inability to disrupt SERA5 and the apparent compensatory increase in SERA5 expression in response to the deletion of SERA4 provides evidence for an important blood-stage function for the serine-type SERAs and supports the notion of functional redundancy among this group. Such redundancy is consistent with our phylogenetic analysis, which reveals a monophyletic grouping of the serine-type SERAs across the genus Plasmodium and a predominance of postspeciation expansion. While SERA5 is to some extent further validated as a target for vaccine and drug development, our data suggest that the expression level of other serine-type SERAs is the only barrier to escape from anti-SERA5-specific interventions.

Host immune evasion strategies of malaria blood stage parasite

2017 ◽  
Vol 13 (12) ◽  
pp. 2498-2508 ◽  
Author(s):  
Xue Yan Yam ◽  
Peter R. Preiser
Keyword(s):  
Causative Agent ◽  
Immune Evasion ◽  
Blood Stage ◽  
Microbial Pathogens ◽  
Stage Parasite ◽  
Blood Stage Parasite

Host immune evasion is a key strategy for the continual survival of many microbial pathogens including Apicomplexan protozoan:Plasmodiumspp., the causative agent of Malaria.

scholarly journals Baculovirus-Based Nasal Drop Vaccine Confers Complete Protection against Malaria by Natural Boosting of Vaccine-Induced Antibodies in Mice

2009 ◽  
Vol 78 (2) ◽  
pp. 595-602 ◽  
Author(s):  
Shigeto Yoshida ◽  
Hitomi Araki ◽  
Takashi Yokomine
Keyword(s):  
Three Dimensional ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Blood Stage ◽  
Dimensional Structure ◽  
Protective Mechanism ◽  
Complete Protection ◽  
Virus Envelope

ABSTRACT Blood-stage malaria parasites ablate memory B cells generated by vaccination in mice, resulting in diminishing natural boosting of vaccine-induced antibody responses to infection. Here we show the development of a new vaccine comprising a baculovirus-based Plasmodium yoelii 19-kDa carboxyl terminus of merozoite surface protein 1 (PyMSP119) capable of circumventing the tactics of parasites in a murine model. The baculovirus-based vaccine displayed PyMSP119 on the surface of the virus envelope in its native three-dimensional structure. Needle-free intranasal immunization of mice with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titers of PyMSP119-specific antibodies. Most importantly, this vaccine conferred complete protection by natural boosting of vaccine-induced PyMSP119-specific antibody responses shortly after challenge. The protective mechanism is a mixed Th1/Th2-type immunity, which is associated with the Toll-like receptor 9 (TLR9)-dependent pathway. The present study offers a novel strategy for the development of malaria blood-stage vaccines capable of naturally boosting vaccine-induced antibody responses to infection.

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