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Frontiers in Immunology 2019In the development of vaccines, the ability to initiate both innate and subsequent adaptive immune responses need to be considered. Live attenuated vaccines achieve this... (Review)
Review
In the development of vaccines, the ability to initiate both innate and subsequent adaptive immune responses need to be considered. Live attenuated vaccines achieve this naturally, while inactivated and sub-unit vaccines generally require additional help provided through delivery systems and/or adjuvants. Liposomes present an attractive adjuvant/delivery system for antigens. Here, we review the key aspects of immunity against parasites, liposome design considerations and their current application in the development of a malaria vaccine.
Topics: Animals; Humans; Liposomes; Malaria Vaccines; Plasmodium
PubMed: 30774635
DOI: 10.3389/fimmu.2019.00135 -
The Indian Journal of Medical Research Jun 2016Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens... (Review)
Review
Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.
Topics: Adjuvants, Immunologic; Animals; Antigens, Protozoan; Culicidae; Humans; Immunity, Innate; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 27748294
DOI: 10.4103/0971-5916.191927 -
Trends in Parasitology Jun 2020Despite ongoing efforts, a highly effective vaccine against Plasmodium falciparum remains elusive. Vaccines targeting the pre-erythrocytic stages of the P. falciparum... (Review)
Review
Despite ongoing efforts, a highly effective vaccine against Plasmodium falciparum remains elusive. Vaccines targeting the pre-erythrocytic stages of the P. falciparum life cycle are the most advanced to date, affording moderate levels of efficacy in field trials. However, the discovery that the members of the merozoite PfRH5-PfCyRPA-PfRipr (RCR) complex are capable of inducing strain-transcendent neutralizing antibodies has renewed enthusiasm for the possibility of preventing disease by targeting the parasite during the blood stage of infection. With Phase I/II clinical trials now underway using first-generation vaccines against PfRH5, and more on the horizon for PfCyRPA and PfRipr, this review explores the rationale and future potential of the RCR complex as a P. falciparum vaccine target.
Topics: Antibodies, Neutralizing; Antigens, Protozoan; Carrier Proteins; Clinical Trials as Topic; Malaria; Malaria Vaccines; Plasmodium falciparum; Protozoan Proteins
PubMed: 32359873
DOI: 10.1016/j.pt.2020.04.003 -
Vaccine Feb 2023The World Health Organization (WHO) recommended widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children residing in regions of moderate to high malaria...
BACKGROUND
The World Health Organization (WHO) recommended widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children residing in regions of moderate to high malaria transmission. This recommendation is informed by RTS,S evidence, including findings from the pilot rollout of the vaccine in Ghana, Kenya, and Malawi. This study estimates the incremental costs of introducing and delivering the malaria vaccine within routine immunization programs in the context of malaria vaccine pilot introduction, to help inform decision-making.
METHODS
An activity-based, retrospective costing was conducted from the governments' perspective. Vaccine introduction and delivery costs supported by the donors during the pilot introduction were attributed as costs to the governments under routine implementation. Detailed resource use data were extracted from the pilot program expenditure and activity reports for 2019-2021. Primary data from representative health facilities were collected to inform recurrent operational and service delivery costs.Costs were categorized as introduction or recurrent costs. Both financial and economic costs were estimated and reported in 2020 USD. The cost of donated vaccine doses was evaluated at $2, $5 and $10 per dose and included in the economic cost estimates. Financial costs include the procurement add on costs for the donated vaccines and immunization supplies, along with other direct expenses.
FINDINGS
At a vaccine price of $5 per dose, the incremental cost per dose administered across countries ranges from $2.30 to $3.01 (financial), and $8.28 to $10.29 (economic). The non-vaccine cost of delivery ranges between $1.04 and $2.46 (financial) and $1.52 and $4.62 (economic), by country. Considering only recurrent costs, the non-vaccine cost of delivery per dose ranges between $0.29 and $0.89 (financial) and $0.59 and $2.29 (economic), by country. Introduction costs constitute between 33% and 71% of total financial costs. Commodity and procurement add-on costs are the main cost drivers of total cost across countries. Incremental resource needs for implementation are dependent on country's baseline immunization program capacity constraints.
INTERPRETATION
The financial costs of introducing RTS,S are comparable with costs of introducing other new vaccines. Country resource requirements for malaria vaccine introduction are most influenced by vaccine price and potential donor funding for vaccine purchases and introduction support.
Topics: Child; Humans; Malaria Vaccines; Retrospective Studies; Malaria; Vaccination; Immunization Programs
PubMed: 36710234
DOI: 10.1016/j.vaccine.2023.01.043 -
Vaccine Jun 2016Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200...
Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding.
Topics: Animals; Biomedical Research; Clinical Trials as Topic; Culicidae; Humans; Malaria; Malaria Vaccines
PubMed: 26993333
DOI: 10.1016/j.vaccine.2015.12.074 -
Parasites & Vectors Dec 2023Despite years of effort to develop an effective vaccine against malaria infection, a vaccine that provides individuals with sufficient protection against malaria illness...
BACKGROUND
Despite years of effort to develop an effective vaccine against malaria infection, a vaccine that provides individuals with sufficient protection against malaria illness and death in endemic areas is not yet available. The development of transmission-blocking vaccines (TBVs) is a promising strategy for malaria control. A dual-antigen malaria vaccine targeting both pre- and post-fertilization antigens could effectively improve the transmission-blocking activity of vaccines against the sexual stages of the parasite.
METHODS
A chimeric recombinant protein Pb22-Pbg37 (Plasmodium berghei 22-P. berghei G37) composed of 19-218 amino acids (aa) of Pb22 and the N-terminal 26-88 aa of Pbg37 was designed and expressed in the Escherichia coli expression system. The antibody titers of the fusion (Pb22-Pbg37) and mixed (Pb22+Pbg37) antigens, as well as those of Pb22 and Pbg37 single antigens were evaluated by enzyme-linked immunosorbent assay. Immunofluorescence and western blot assays were performed to test the reactivity of the antisera with the native proteins in the parasite. The induction of transmission-blocking activity (TBA) by Pb22-Pbg37 and Pb22+Pbg37 were evaluated by in vitro gametocyte activation, gamete and exflagellation center formation, ookinete conversion, and in the direct mosquito feeding assay.
RESULTS
The Pb22-Pbg37 fusion protein was successfully expressed in vitro. Co-administration of Pb22 and Pbg37 as a fusion or mixed protein elicited comparable antibody responses in mice and resulted in responses to both antigens. Most importantly, both the mixed and fusion antigens induced antibodies with significantly higher levels of TBA than did each of the individual antigens when administered alone. In addition, the efficacy of vaccination with the Pb22-Pbg37 fusion protein was equivalent to that of vaccination with the mixed single antigens.
CONCLUSIONS
Dual-antigen vaccines, which expand/lengthen the period during which the transmission-blocking antibodies can act during sexual-stage development, can provide a promising higher transmission-reducing activity compared to single antigens.
Topics: Mice; Animals; Malaria Vaccines; Protozoan Proteins; Malaria; Vaccination; Recombinant Proteins; Antibodies, Protozoan; Antigens, Protozoan; Plasmodium falciparum
PubMed: 38098083
DOI: 10.1186/s13071-023-06071-x -
Expert Review of Vaccines Feb 2021causes significant public health problems in endemic regions. A vaccine to prevent disease is critical, considering the rapid spread of drug-resistant parasite strains,... (Review)
Review
INTRODUCTION
causes significant public health problems in endemic regions. A vaccine to prevent disease is critical, considering the rapid spread of drug-resistant parasite strains, and the development of hypnozoites in the liver with potential for relapse. A minimally effective vaccine should prevent disease and transmission while an ideal vaccine provides sterile immunity.
AREAS COVERED
Despite decades of research, the complex life cycle, technical challenges and a lack of funding have hampered progress of vaccine development. Here, we review the progress of potential vaccine candidates from different stages of the parasite life cycle. We also highlight the challenges and important strategies for rational vaccine design. These factors can significantly increase immune effector mechanisms and improve the protective efficacy of these candidates in clinical trials to generate sustained protection over longer periods of time.
EXPERT OPINION
A vaccine that presents functionally-conserved epitopes from multiple antigens from various stages of the parasite life cycle is key to induce broadly neutralizing strain-transcending protective immunity to effectively disrupt parasite development and transmission.
Topics: Animals; Antigens, Protozoan; Drug Resistance; Humans; Liver; Malaria Vaccines; Malaria, Vivax; Plasmodium vivax; Recurrence; Time Factors
PubMed: 33481638
DOI: 10.1080/14760584.2021.1880898 -
Vaccine Dec 2015Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to... (Review)
Review
Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication.
Topics: Adult; Africa; Clinical Trials as Topic; Cryopreservation; Disease Eradication; Europe; Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Sporozoites; Vaccine Potency; Vaccines, Attenuated
PubMed: 26469720
DOI: 10.1016/j.vaccine.2015.09.096 -
Frontiers in Cellular and Infection... 2017Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including... (Review)
Review
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including species, the causative agents of malaria. Efficient elimination of liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in and and compare their vaccine potential. A better understanding of the immunological mechanisms of prime and boost by arrested sporozoites and experimental strategies to enhance vaccine efficacy by further engineering existing GAPs into a more immunogenic form hold promise for continuous improvements of GAP-based vaccines. A critical hurdle for vaccines that elicit long-lasting protection against malaria, such as GAPs, is safety and efficacy in vulnerable populations. Vaccine research should focus on solutions toward turning malaria into a vaccine-preventable disease, which would offer an exciting new path of malaria control.
Topics: Animals; CD8-Positive T-Lymphocytes; Gene Deletion; Humans; Liver; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium; Plasmodium berghei; Sporozoites; Vaccination; Vaccines, Attenuated
PubMed: 28620583
DOI: 10.3389/fcimb.2017.00198 -
Health Expectations : An International... Dec 2023Malaria exists as an endemic in many countries including Bangladesh and the malaria vaccine is not yet available here. The study aimed to assess the level of knowledge...
BACKGROUND
Malaria exists as an endemic in many countries including Bangladesh and the malaria vaccine is not yet available here. The study aimed to assess the level of knowledge and acceptance of the malaria vaccination among the parents of children under the age of five in Bangladesh's malaria-endemic areas and the sociodemographic, behavioural, and household factors associated with the acceptance and knowledge of the malaria vaccine.
METHODS
From January to March 2022, a cross-sectional study was conducted in all five malaria-endemic districts of Bangladesh, involving 405 parents of children under the age of 5 who met the inclusion criteria. Multiple logistic regression was used to analyze the factor affecting parents' acceptance and knowledge of malaria vaccination in children under five and other variables.
RESULTS
Majority (54%) of the respondents were mothers. Almost half (49%) of the respondents were aged between 26 and 35 years old and around 90% were from rural areas. A small portion (20%) of the participants were housewives and 46% of them completed primary education. Overall, 70% of the study participants reported that they would accept malaria vaccination independently. About one-fourth (25%) heard about the malaria vaccine and 48% of them mentioned health professionals as the source of information. Knowledge of malaria vaccination was found associated with residence, income, and family size. Acceptance and knowledge were both associated with residence, education, occupation, income, and family size. In a multivariable analysis, housing structure, house wall, house window, knowledge of malaria, testing for malaria, and being diagnosed with malaria were all associated with knowledge of and acceptance of getting vaccinated against malaria.
CONCLUSIONS
The present study highlights the necessity of creating awareness of malaria vaccines in epidemic areas of Bangladesh. This study offers crucial data to develop a policy for a novel malaria vaccine, supporting its adoption in Bangladesh.
PUBLIC CONTRIBUTION
This study was based on interviews. The interviewees were recruited as public representatives from the malaria-endemic area to assist us in building an understanding of knowledge and acceptance of the malaria vaccine among parents of under-five children in Bangladesh.
Topics: Female; Humans; Child; Adult; Malaria Vaccines; Cross-Sectional Studies; Bangladesh; Vaccination; Parents; Malaria; Health Knowledge, Attitudes, Practice
PubMed: 37661603
DOI: 10.1111/hex.13862