| Autor: |
Richie TL; Naval Medical Research Center; Silver Spring, MD, USA. Thomas.Richie@med.navy.mil, Charoenvit Y, Wang R, Epstein JE, Hedstrom RC, Kumar S, Luke TC, Freilich DA, Aguiar JC, Sacci JB Jr, Sedegah M, Nosek RA Jr, De La Vega P, Berzins MP, Majam VF, Abot EN, Ganeshan H, Richie NO, Banania JG, Baraceros MF, Geter TG, Mere R, Bebris L, Limbach K, Hickey BW, Lanar DE, Ng J, Shi M, Hobart PM, Norman JA, Soisson LA, Hollingdale MR, Rogers WO, Doolan DL, Hoffman SL |
| Jazyk: |
angličtina |
| Zdroj: |
Human vaccines & immunotherapeutics [Hum Vaccin Immunother] 2012 Nov 01; Vol. 8 (11), pp. 1564-84. Date of Electronic Publication: 2012 Nov 01. |
| DOI: |
10.4161/hv.22129 |
| Abstrakt: |
When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997-1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000-2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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