Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus

Abstract

Multiagent DNA vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. Few animal studies have compared the feasibility of combining unrelated gene vaccines. Here, we demonstrate that DNA vaccines to four dissimilar pathogens that are known biowarfare agents, Bacillus anthracis, Ebola (EBOV), Marburg (MARV), and Venezuelan equine encephalitis virus (VEEV), can elicit protective immunity in relevant animal models. In addition, a combination of all four vaccines is shown to be equally as effective as the individual vaccines for eliciting immune responses in a single animal species. These results demonstrate for the first time the potential of combined DNA vaccines for these agents and point to a possible method of rapid development of multiagent vaccines for disparate pathogens such as those that might be encountered in a biological attack.

How Ebola and Marburg viruses battle the immune system

“…Put most simply, higher doses of vaccine seem to evoke greater total immune responses, along with a protection that is more rapidly acquired and more complete than that obtained with replication-defective vaccines given at much lower doses. A recent report with a recombinant adenovirus that expresses the ZEBOV glycoprotein, in which the minimal protective dose of 10 10 particles is described as a 'low dose' , affirms that protection is dependent on the vaccine dose 65 , and might explain why repliconbased vaccines given at much lower doses have not been uniformly successful 67 and DNA vaccines have been only partially effective 79 . Live vesicular stomatitis virus (VSV) 64 or parainfluenza virus 80,81 recombinants, which show considerable promise in protecting non-human primates from filoviral infection, presumably generate high amounts of viral glycoprotein antigen in vivo.…”

Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

“…[17][18][19][20][21] In earlier studies, we showed that DNA vaccines expressing the GP genes of MARV delivered by gene gun elicited partially protective immunity in NHP. 22 Similarly, we showed that an EBOV GP DNA vaccine delivered to guinea pigs by gene gun provided partial protection against EBOV challenge. 23 Toward the goal of improving the protective efficacy of these DNA vaccines, we designed gene-optimized DNA vaccine constructs and used a more potent delivery method, intramuscular electroporation (IM-EP).…”

“…22 We also tested a similar EBOV DNA vaccine, using a prime-boost regimen with a DNA prime and a baculovirus-expressed EBOV GP boost. Although this approach was successful for MARV in guinea pigs and nonhuman primates (NHP), it was not successful for conferring protective immunity against EBOV.…”

Status and challenges of filovirus vaccines

“…In guinea pigs, a DNA vaccine expressing MARV GP was weakly immunogenic compared to other strategies and offered incomplete protection when given alone but worked well when boosted with baculovirus-expressed GP TM [60]. In NHP, the DNA MARV GP vaccine protected four of six cynomolgus macaques from lethal MARV infection [80]. In mice, a DNA vaccine expressing GP from ZEBOV was able to fully protect mice against ZEBOV challenge [80] but failed to adequately protect guinea pigs [79].…”

“…In NHP, the DNA MARV GP vaccine protected four of six cynomolgus macaques from lethal MARV infection [80]. In mice, a DNA vaccine expressing GP from ZEBOV was able to fully protect mice against ZEBOV challenge [80] but failed to adequately protect guinea pigs [79]. Another DNA vaccine construct, however, was successful in protecting guinea pigs against ZEBOV challenge [81].…”