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A DNA Vaccine Encoding Plasmodium falciparum PfRH5 in Cationic Liposomes for Dermal Tattooing Immunization

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Autor(es):
Fotoran, Wesley Luzetti [1] ; Kleiber, Nicole [1] ; Glitz, Christiane [2] ; Wunderlich, Gerhard [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed 2, Dept Parasitol, BR-05508000 Sao Paulo - Brazil
[2] Westfalische Wilhelms Univ Munster, Inst Anim Physiol, Dept Mol Physiol, D-48149 Munster - Germany
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: VACCINES; v. 8, n. 4 DEC 2020.
Citações Web of Science: 0
Resumo

Vaccines are the primary means of controlling and preventing pandemics and outbreaks of pathogens such as bacteria, viruses, and parasites. However, a major drawback of naked DNA-based vaccines is their low immunogenicity and the amount of plasmid DNA necessary to elicit a response. Nano-sized liposomes can overcome this limitation, enhancing both nucleic acid stability and targeting to cells after administration. We tested two different DNA vaccines in cationic liposomes to improve the immunogenic properties. For this, we cloned the coding sequences of the Plasmodium falciparum reticulocyte binding protein homologue 5 (PfRH5) either alone or fused with small the small hepatitis virus (HBV) envelope antigen (HBsAg) encoding sequences, potentially resulting in HBsAg particles displaying PfRH5 on their outside. Instead of invasive intraperitoneal or intramuscular immunization, we employed intradermal immunization by tattooing nano-encapsulated DNA. Mice were immunized with 10 mu g encapsulated DNA encoding PfRH5 alone or in fusion with HBsAg and this elicited antibodies against schizont extracts (titer of 10(4)). Importantly, only IgG from animals immunized with PfRH5-HBs demonstrated sustained IgG-mediated inhibition in in vitro growth assays showing 58% and 39% blocking activity after 24 and 48 h, respectively. Intradermal tattoo-vaccination of encapsulated PfRH5-HBsAg coding plasmid DNA is effective and superior compared with an unfused PfRH5-DNA vaccine, suggesting that the HBsAg fusion may be advantageous with other vaccine antigens. (AU)

Processo FAPESP: 15/17174-7 - Avaliação de fatores que influem na expressão de famílias multigênicas var, rif e surf de P. falciparum, o parasita da malária humana
Beneficiário:Gerhard Wunderlich
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/24267-7 - Papel de modificadores de cromatina na dinâmica da transcrição de fatores de virulência no parasita da Malária Plasmodium falciparum
Beneficiário:Gerhard Wunderlich
Modalidade de apoio: Auxílio à Pesquisa - Regular