DNA-Loaded Cationic Liposomes Efficiently Function as a Vaccine against Malarial Proteins

Author(s)

Fotoran, Wesley L. ^[1] ; Santangelo, Rachele ^[1] ; de Mirand, Beatriz N. M. ^[2] ; Irvine, Darrell J. ^{[3, 4, 5, 6, 7]} ; Wunderlich, Gerhard ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Chem Sao Carlos, Av Trabalhador Sao Carlense 400, BR-13566590 Sao Carlos, SP - Brazil

^[3] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 - USA

^[4] Howard Hughes Med Inst, Chevy Chase, MD - USA

^[5] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[6] MIT, Dept Biomed Engn, 77 Massachusetts Ave, Cambridge, MA 02139 - USA

^[7] Ragon Inst MGH & Harvard Univ, Boston, MA - USA

• Document type: Journal article
• Source: MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT; v. 7, p. 1-10, DEC 2017.
• Web of Science Citations: 4

Abstract

The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures. The liposome-based approach provided strong humoral responses against three malarial antigens, namely the Circumsporozoite protein and the C terminus of merozoite surface protein 1 from Plasmodium vivax (titers 10(4) or 10(3)-10(4), respectively) and P. falciparum Rhoptry antigen 5 from Plasmodium falciparum (titers 10(3)-10(4)). When employed in P. falciparum growth-inhibition assays, antibodies demonstrated consistent reinvasion-blocking activities that were dose dependent. Liposome-formulated DNA vaccines may prove useful when targets cannot be produced as recombinant proteins and when conformation-dependent and highly specific antibodies are mandatory. (AU)

• FAPESP's process: 12/18617-1 - Role of variant antigens in the immunity against murine Plasmodium: Estimating the influence of variant proteins BIR in cytoadherence and their potential as vaccine using novel means of administration.
• Grantee: Wesley Luzetti Fotoran
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/17174-7 - Factors influencing expression of variant antigen families var, rif and surf of Plasmodium falciparum, the human malaria parasite
• Grantee: Gerhard Wunderlich
• Support Opportunities: Regular Research Grants