A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892-3017, United States.
Vaccine (Impact Factor: 3.49). 10/2010; 29(2):304-13. DOI: 10.1016/j.vaccine.2010.10.037
Source: PubMed

ABSTRACT Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2×10(9) (n=12), or 2×10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses.

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    • "Using Ad vectors derived from a variety of serotypes, families, or species showed consistently that they induced potent transgene productspecific B and CD8 + T cell responses. Several Ad vectors are in clinical trials as vaccine carriers for antigens of HIV-1 (Catanzaro et al., 2006; Baden et al., 2012), Mycobacterium tuberculosis (Hoft et al., 2012), hepatitis C virus (Barnes et al., 2012), Ebola virus (Ledgerwood et al., 2010), influenza virus (Gurwith et al., 2013), and Plasmodium falciparum (Sheehy et al., 2012). One Ad vaccine vector, based on a replication-competent E3-deleted Ad vector of human serotype 5 (HAdV-5) expressing the rabies virus glycoprotein for immunization of wildlife animals, has been licensed (Mainguy et al., 2013). "
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