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1.
EBioMedicine ; 42: 145-156, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30885725

RESUMO

BACKGROUND: VAR2CSA is the lead antigen for developing a vaccine that would protect pregnant women against placental malaria. A multi-system feasibility study has identified E. coli as a suitable bacterial expression platform allowing the production of recombinant VAR2CSA-DBL1x-2x (PRIMVAC) to envisage a prompt transition to current Good Manufacturing Practice (cGMP) vaccine production. METHODS: Extensive process developments were undertaken to produce cGMP grade PRIMVAC to permit early phase clinical trials. PRIMVAC stability upon storage was assessed over up to 3 years. A broad toxicology investigation was carried out in rats allowing meanwhile the analysis of PRIMVAC immunogenicity. FINDINGS: We describe the successful cGMP production of 4. 65 g of PRIMVAC. PRIMVAC drug product was stable and potent for up to 3 years upon storage at -20 °C and showed an absence of toxicity in rats. PRIMVAC adjuvanted with Alhydrogel® or GLA-SE was able to generate antibodies able to recognize VAR2CSA expressed at the surface of erythrocytes infected with different strains. These antibodies also inhibit the interaction of the homologous NF54-CSA strain and to a lower extend of heterologous strains to CSA. INTERPRETATION: This work paved the way for the clinical development of an easily scalable low cost effective vaccine that could protect against placental malaria and prevent an estimated 10,000 maternal and 200,000 infant deaths annually. FUND: This work was supported by a grant from the Bundesministerium für Bildung und Forschung (BMBF), Germany through Kreditanstalt für Wiederaufbau (KfW) (Reference No: 202060457) and through funding from Irish Aid, Department of Foreign Affairs and Trade, Ireland.


Assuntos
Imunogenicidade da Vacina , Vacinas Antimaláricas/imunologia , Malária/imunologia , Malária/prevenção & controle , Animais , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Biomarcadores , Reações Cruzadas/imunologia , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/imunologia , Feminino , Imunização , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/normas , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Masculino , Camundongos
2.
Malar J ; 16(1): 263, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28673287

RESUMO

BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors. RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen. CONCLUSION: These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development.


Assuntos
Adenovirus dos Símios , Vetores Genéticos/normas , Vacinas Antimaláricas/imunologia , Malária/prevenção & controle , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Adenovirus dos Símios/genética , Adenovirus dos Símios/imunologia , Animais , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Feminino , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Gana/epidemiologia , Gorilla gorilla , Humanos , Interferon gama/sangue , Quênia/epidemiologia , Malária/epidemiologia , Vacinas Antimaláricas/normas , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos , Plasmodium yoelii/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Estudos Soroepidemiológicos , Baço/citologia , Baço/imunologia , Linfócitos T/imunologia , Transgenes/imunologia , Estados Unidos/epidemiologia
3.
Trends Parasitol ; 33(3): 154-156, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28169112

RESUMO

Vaccines that do not take a comprehensive endpoint view of the pathogen population they want to tackle early in their developmental process, may find it financially prohibitive to redesign them once they have progressed down a costly regulatory and human trial pathway. Specifically, the lead malaria vaccine candidate RTS,S has limited ability to tackle parasite polymorphism and may induce sex-specific nonspecific effects (NSEs).


Assuntos
Vacinas Antimaláricas/economia , Vacinas Antimaláricas/normas , Malária/economia , Malária/prevenção & controle , Ensaios Clínicos como Assunto , Humanos , Imunidade Heteróloga , Fatores Sexuais
4.
Trends Parasitol ; 33(3): 202-213, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27793562

RESUMO

Immunization with malaria parasites that developmentally arrest in or immediately after the liver stage is the only way currently known to confer sterilizing immunity in both humans and rodent models. There are various ways to attenuate parasite development resulting in different timings of arrest, which has a significant impact on vaccination efficiency. To understand what most impacts vaccination efficiency, newly developed gain-of-function methods can now be used to generate a wide array of differently attenuated parasites. The combination of multiple attenuation approaches offers the potential to engineer efficiently attenuated Plasmodium parasites and learn about their fascinating biology at the same time. Here we discuss recent studies and the potential of targeted parasite manipulation using genome editing to develop live attenuated malaria vaccines.


Assuntos
Edição de Genes , Imunização/tendências , Vacinas Antimaláricas/imunologia , Malária/prevenção & controle , Plasmodium/genética , Plasmodium/imunologia , Animais , Humanos , Malária/imunologia , Malária/parasitologia , Vacinas Antimaláricas/normas , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/normas
5.
Trends Parasitol ; 32(4): 284-295, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26778295

RESUMO

A highly-effective, long-lasting vaccine, targeting multiple stages of the Plasmodium falciparum life cycle, is likely to be important for the elimination of this pathogen. Key antigens of this vaccine would produce host antibodies that block the ligands required for merozoite invasion of erythrocytes, thereby curtailing the expansion of parasitemia and symptomatic disease. Recent live cell imaging of invading Plasmodium falciparum merozoites with various receptor-ligand interactions inhibited has provided new information about the function, sequence, and timing of these events, providing a rationale for a vaccine containing multiple antigens that inhibit the sequential steps of invasion.


Assuntos
Eritrócitos/parasitologia , Malária Falciparum/fisiopatologia , Plasmodium falciparum/fisiologia , Humanos , Estágios do Ciclo de Vida/fisiologia , Ligantes , Vacinas Antimaláricas/normas , Plasmodium falciparum/genética , Proteínas de Protozoários/genética
6.
Adv Parasitol ; 89: 109-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26003037

RESUMO

Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches.


Assuntos
Vacinas Antimaláricas , Malária/prevenção & controle , Animais , Ensaios Clínicos como Assunto , Culicidae/genética , Culicidae/metabolismo , Humanos , Proteínas de Insetos/imunologia , Estágios do Ciclo de Vida , Malária/transmissão , Vacinas Antimaláricas/economia , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/normas , Plasmodium/imunologia , Plasmodium/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia
7.
Adv Parasitol ; 88: 1-49, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25911364

RESUMO

The development of a highly effective malaria vaccine remains a key goal to aid in the control and eventual eradication of this devastating parasitic disease. The field has made huge strides in recent years, with the first-generation vaccine RTS,S showing modest efficacy in a Phase III clinical trial. The updated 2030 Malaria Vaccine Technology Roadmap calls for a second generation vaccine to achieve 75% efficacy over two years for both Plasmodium falciparum and Plasmodium vivax, and for a vaccine that can prevent malaria transmission. Whole-parasite immunisation approaches and combinations of pre-erythrocytic subunit vaccines are now reporting high-level efficacy, whilst exciting new approaches to the development of blood-stage and transmission-blocking vaccine subunit components are entering clinical development. The development of a highly effective multi-component multi-stage subunit vaccine now appears to be a realistic ambition. This review will cover these recent developments in malaria vaccinology.


Assuntos
Imunização/tendências , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/normas , Animais , Humanos , Malária/prevenção & controle , Esporozoítos/imunologia , Vacinas de Subunidades/imunologia
8.
Vaccine ; 33(13): 1518-26, 2015 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-25681064

RESUMO

Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist.


Assuntos
Ensaios Clínicos Fase III como Assunto , Vacinas Antimaláricas , Malária Falciparum/prevenção & controle , Malária Falciparum/transmissão , Animais , Humanos , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/normas , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/imunologia , Vigilância de Evento Sentinela
9.
Ned Tijdschr Geneeskd ; 159: A9730, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-26732220

RESUMO

RTS,S is the first vaccine to have received a positive opinion from the European Medicines Agency (EMA) under Article 58, for vaccination of young children aged from 6 weeks up to 17 months against malaria caused by Plasmodium falciparum and against hepatitis B. Although vaccine efficacy is modest and wanes rapidly, a substantial number of cases of clinical malaria can be averted, particularly in settings with high disease burden. Further evaluations are needed regarding safety, and more specifically regarding efficacy against severe malaria and mortality. The current formulation, however, is a milestone as a gold standard and represents a basis for further required improvements. Evaluation of the benefits, risks and feasibility are anticipated at global and national levels.


Assuntos
Vacinas Antimaláricas/administração & dosagem , Malária/prevenção & controle , Humanos , Lactente , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/normas , Malária Falciparum/prevenção & controle , Plasmodium falciparum , Medição de Risco , Vacinação
10.
Vaccine ; 32(48): 6556-62, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25077418

RESUMO

BACKGROUND: For regulatory approval, consistency in manufacturing of vaccine lots is expected to be demonstrated in confirmatory immunogenicity studies using two-sided equivalence trials. This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced. METHODS: Healthy children aged 5-17 months were randomized (1:1:1:1) to receive RTS,S/AS01 at 0-1-2 months from one of three commercial-scale purified antigen bulk lots (1600 litres-fermentation scale; commercial-scale lots), or a comparator vaccine batch made from pilot-scale purified antigen bulk lot (20 litres-fermentation scale; pilot-scale lot). The co-primary objectives were to first demonstrate consistency of antibody responses against circumsporozoite (CS) protein at one month post-dose 3 for the three commercial-scale lots and second demonstrate non-inferiority of anti-CS antibody responses at one month post-dose 3 for the commercial-scale lots compared to the pilot-scale lot. Safety and reactogenicity were evaluated as secondary endpoints. RESULTS: One month post-dose-3, anti-CS antibody geometric mean titres (GMT) for the 3 commercial scale lots were 319.6 EU/ml (95% confidence interval (CI): 268.9-379.8), 241.4 EU/ml (207.6-280.7), and 302.3 EU/ml (259.4-352.3). Consistency for the RTS,S/AS01 commercial-scale lots was demonstrated as the two-sided 95% CI of the anti-CS antibody GMT ratio between each pair of lots was within the range of 0.5-2.0. GMT of the pooled commercial-scale lots (285.8 EU/ml (260.7-313.3)) was non-inferior to the pilot-scale lot (271.7 EU/ml (228.5-323.1)). Each RTS,S/AS01 lot had an acceptable tolerability profile, with infrequent reports of grade 3 solicited symptoms. No safety signals were identified and no serious adverse events were considered related to vaccination. CONCLUSIONS: RTS,S/AS01 lots formulated from commercial-scale purified antigen bulk batches induced a consistent anti-CS antibody response, and the anti-CS GMT of pooled commercial-scale lots was non-inferior to that of a lot formulated from a pilot-scale antigen bulk batch.


Assuntos
Formação de Anticorpos , Vacinas Antimaláricas/normas , Vacinas Antimaláricas/uso terapêutico , Malária Falciparum/prevenção & controle , Vacinas Sintéticas/normas , Vacinas Sintéticas/uso terapêutico , Anticorpos Antiprotozoários/sangue , Método Duplo-Cego , Feminino , Humanos , Lactente , Vacinas Antimaláricas/imunologia , Masculino , Nigéria , Vacinas Sintéticas/imunologia
11.
Vaccine ; 32(35): 4365-8, 2014 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-24950356

RESUMO

High-throughput analyses of RNA and protein expression are increasingly used for better understanding of vaccine-induced immunity and protection against infectious disease. With an increasing number of vaccine candidates in clinical development, it is timely to consider standardisation and harmonisation of sample collection, storage and analysis to ensure results of highest quality from these precious samples. These challenges were discussed by a group of international experts during a workshop organised by TRANSVAC, a European Commission-funded Research Infrastructure project. The main conclusions were: Platforms are rarely standardised for use in preclinical and clinical studies. Coordinated efforts should continue to harmonise the experimental set up of these studies, as well as the establishment of internal standards and controls. This will ensure comparability, efficiency and feasibility of the global analyses performed on preclinical and clinical data sets.


Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/normas , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/normas , Vacinas contra a Tuberculose/imunologia , Vacinas contra a Tuberculose/normas , Vacinação/normas , Pesquisa Biomédica/normas , Humanos , Vacinação/métodos
12.
BMC Med ; 11: 232, 2013 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-24228861

RESUMO

BACKGROUND: Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. DISCUSSION: The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. CONCLUSIONS: Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.


Assuntos
Ensaios Clínicos como Assunto/legislação & jurisprudência , Ensaios Clínicos como Assunto/métodos , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/normas , Malária/prevenção & controle , Austrália , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
14.
Exp Parasitol ; 135(3): 546-50, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24055215

RESUMO

No licensed malaria vaccine exists, in spite of intensive development efforts. We have been investigating development of a DNA vaccine to prevent malaria infection. To date, we have established a full-length cDNA expression library from the erythrocytic-stage murine malaria parasite, Plasmodium berghei. We found that immunization of mice with combined 2000 clones significantly prolonged survival after challenge infection and that splenocytes from the immunized mice showed parasite-specific cytokine production. We determined the 5'-end one-pass sequence of these clones and mapped a draft genomic sequence for P. berghei for use in screening vaccine candidates for efficacy. In this study, we annotated these cDNA clones by comparing them with the genomic sequence of Plasmodium falciparum. We then divided them into several subsets based on their characteristics and examined their protective effects against malaria infection. Consequently, we selected 104 clones that strongly induced specific IgG production and decreased the mortality rate in the early phase. Most of these 104 clones coded for unknown proteins. The results suggest that these clones represent potential novel malaria vaccine candidates.


Assuntos
Vacinas Antimaláricas/normas , Malária/prevenção & controle , Plasmodium berghei/imunologia , Vacinas de DNA/normas , Animais , Biolística , Mapeamento Cromossômico , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Genoma de Protozoário/genética , Genoma de Protozoário/imunologia , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Plasmídeos/genética , Plasmídeos/imunologia , Plasmodium berghei/genética , Ratos , Ratos Wistar , Organismos Livres de Patógenos Específicos
17.
Int J Parasitol ; 42(9): 859-70, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22846785

RESUMO

A promising strategy for the development of a malaria vaccine involves the use of attenuated whole parasites, as these present a greater repertoire of antigens to the immune system than subunit vaccines. The complexity of the malaria parasite's life cycle offers multiple stages on which to base an attenuated whole organism vaccine. An important consideration in the design and employment of such vaccines is the diversity of the parasites that are infective to humans. The most valuable vaccine would be one that was effective against multiple species/strains of malaria parasite. Here we compare the species specificity of pre-erythrocytic and erythrocytic whole organism vaccination using live parasites with anti-malarial drug attenuation. The cross-stage protection afforded by each vaccination strategy, and the possibility that immunity against one stage may be abrogated by exposure to other stages of both homologous and heterologous parasites was also assessed. The rodent malaria parasites Plasmodium yoelii yoelii and Plasmodium vinckei lentum are to address these questions, as they offer the widest possible genetic distance between sub-species of malaria parasites infectious to rodents. It was found that both erythrocytic and pre-erythrocytic stage immunity generated by live, attenuated parasite vaccination have species-specific components, with pre-erythrocytic stage immunity offering a much broader pan-species protection. We show that the protection achieved following sporozoite inoculation with concurrent mefloquine treatment is almost entirely dependent of CD8(+) T-cells. Evidence is presented for cross-stage protection between erythrocytic and pre-erythrocytic stage vaccination. Finally, it is shown that, with these species, an erythrocytic stage infection of either a homologous or heterologous species following immunisation with pre-erythrocytic stages does not abrogate this immunity. This is the first direct comparison of the specificity and efficacy of erythrocytic and pre-erythrocytic stage whole organism vaccination strategies utilising the same parasite species pair.


Assuntos
Vacinas Antimaláricas/imunologia , Plasmodium/classificação , Plasmodium/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Linfócitos T CD8-Positivos/imunologia , Eritrócitos/parasitologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Vacinas Antimaláricas/normas , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia , Plasmodium/genética , RNA de Protozoário/genética , Reação em Cadeia da Polimerase em Tempo Real , Especificidade da Espécie , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/normas
18.
PLoS One ; 7(6): e38434, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22701640

RESUMO

BACKGROUND: Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility. METHODS: We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program. RESULTS: We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates. CONCLUSIONS: Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.


Assuntos
Ensaios Clínicos como Assunto/métodos , Experimentação Humana/normas , Vacinas Antimaláricas/farmacologia , Malária Falciparum/patologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/crescimento & desenvolvimento , Adulto , Análise de Variância , Ensaios Clínicos como Assunto/normas , Feminino , Experimentação Humana/estatística & dados numéricos , Humanos , Vacinas Antimaláricas/normas , Masculino , Pessoa de Meia-Idade , Parasitemia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase/métodos , Estatísticas não Paramétricas
19.
Vaccine ; 30(36): 5302-4, 2012 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-22659449

RESUMO

Early clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field.


Assuntos
Culicidae , Mordeduras e Picadas de Insetos , Vacinas Antimaláricas/normas , Malária/prevenção & controle , Animais , Humanos , Malária/etiologia , Vacinas Antimaláricas/imunologia
20.
J Infect Dis ; 206(3): 319-23, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22615322

RESUMO

The development of a vaccine against malaria has public health priority. In a controlled setting, preliminary data on the efficacy of Plasmodium falciparum vaccine candidates can be obtained by exposing immunized human volunteers to the bites of laboratory-reared P. falciparum-infected mosquitoes. Using empirical data, we show that these trials, with small numbers of volunteers, are sufficiently powered to detect protective biological effects induced by preerythrocytic and/or blood-stage candidate vaccines if parasitemia is measured daily by quantitative polymerase chain reaction. Sporozoite challenge trials are thus a powerful tool for early selection of candidates that warrant efficacy of trials in the field.


Assuntos
Vacinas Antimaláricas/normas , Malária/prevenção & controle , Plasmodium falciparum/imunologia , Esporozoítos/fisiologia , Animais , Culicidae/parasitologia , Eritrócitos/imunologia , Eritrócitos/parasitologia , Humanos , Mordeduras e Picadas de Insetos/complicações , Insetos Vetores/parasitologia , Malária/sangue , Parasitemia/parasitologia , Parasitemia/prevenção & controle , Plasmodium falciparum/crescimento & desenvolvimento , Esporozoítos/imunologia
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