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1.
Malar J ; 20(1): 322, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284778

RESUMO

BACKGROUND: Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. METHODS: A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. RESULTS: There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6-59-month-olds, 0.26 in 5-17-year-olds, 0.20 in 18-45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6-59-month-olds, 0.10 in 5-17-year-olds, 0.11 in 18-45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. CONCLUSION: Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.


Assuntos
Malária Falciparum/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Guiné Equatorial/epidemiologia , Humanos , Incidência , Lactente , Malária Falciparum/parasitologia , Fatores Socioeconômicos , Adulto Jovem
2.
J Exp Med ; 216(8): 1857-1873, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31175140

RESUMO

The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite the central role of Tfh cells in vaccine responses, there is currently no validated way to enhance their differentiation in humans. From paired human lymph node and blood samples, we identify a population of circulating Tfh cells that are transcriptionally and clonally similar to germinal center Tfh cells. In a clinical trial of vaccine formulations, circulating Tfh cells were expanded in Tanzanian volunteers when an experimental malaria vaccine was adjuvanted in GLA-SE but not when formulated in Alum. The GLA-SE-formulated peptide was associated with an increase in the extrafollicular antibody response, long-lived antibody production, and the emergence of public TCRß clonotypes in circulating Tfh cells. We demonstrate that altering vaccine adjuvants is a rational approach for enhancing Tfh cells in humans, thereby supporting the long-lived humoral immunity that is required for effective vaccines.


Assuntos
Adjuvantes Imunológicos/farmacologia , Composição de Medicamentos/métodos , Glucosídeos/farmacologia , Lipídeo A/farmacologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Vacinação/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Hidróxido de Alumínio/farmacologia , Anticorpos Antivirais/efeitos dos fármacos , Anticorpos Antivirais/imunologia , Antígenos de Protozoários/imunologia , Linfócitos B/imunologia , Células Cultivadas , Feminino , Centro Germinativo/imunologia , Humanos , Imunidade Humoral/imunologia , Vacinas contra Influenza/imunologia , Linfonodos/imunologia , Vacinas Antimaláricas/imunologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Adulto Jovem
3.
Clin Infect Dis ; 68(3): 466-474, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29945169

RESUMO

Background: P27A is an unstructured 104mer synthetic peptide from Plasmodium falciparum trophozoite exported protein 1 (TEX1), the target of human antibodies inhibiting parasite growth. The present project aimed at evaluating the safety and immunogenicity of P27A peptide vaccine in malaria-nonexposed European and malaria-exposed African adults. Methods: This study was designed as a staggered, fast-track, randomized, antigen and adjuvant dose-finding, multicenter phase 1a/1b trial, conducted in Switzerland and Tanzania. P27A antigen (10 or 50 µg), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 µg), or control rabies vaccine (Verorab) were administered intramuscularly to 16 malaria-nonexposed and 40 malaria-exposed subjects on days 0, 28, and 56. Local and systemic adverse events (AEs) as well as humoral and cellular immune responses were assessed after each injection and during the 34-week follow-up. Results: Most AEs were mild to moderate and resolved completely within 48 hours. Systemic AEs were more frequent in the formulation with alum as compared to GLA-SE, whereas local AEs were more frequent after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell-mediated immunity, P27A induced a marked specific antibody response able to recognize TEX1 in infected erythrocytes and to inhibit parasite growth through an antibody-dependent cellular inhibition mechanism. Incidence of AEs and antibody responses were significantly lower in malaria-exposed Tanzanian subjects than in nonexposed European subjects. Conclusions: The candidate vaccine P27A was safe and induced a particularly robust immunogenic response in combination with GLA-SE. This formulation should be considered for future efficacy trials. Clinical Trials Registration: NCT01949909, PACTR201310000683408.


Assuntos
Anticorpos Antiprotozoários/sangue , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Hidróxido de Alumínio/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Glucosídeos/administração & dosagem , Voluntários Saudáveis , Humanos , Injeções Intramusculares , Lipídeo A/administração & dosagem , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum , Suíça , Tanzânia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto Jovem
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