A DNA vaccine targeting VEE virus delivered by needle-free jet-injection protects macaques against aerosol challenge

Abstract

We have previously shown that DNA vaccines expressing codon optimized alphavirus envelope glycoprotein genes protect both mice and nonhuman primates from viral challenge when delivered by particle-mediated epidermal delivery (PMED) or intramuscular (IM) electroporation (EP). Another technology with fewer logistical drawbacks is disposable syringe jet injection (DSJI) devices developed by PharmaJet, Inc. These needle-free jet injection systems are spring-powered and capable of delivering vaccines either IM or into the dermis (ID). Here, we evaluated the immunogenicity of our Venezuelan equine encephalitis virus (VEEV) DNA vaccine delivered by either the IM- or ID-DSJI devices in nonhuman primates. The protective efficacy was assessed following aerosol challenge. We found that a prime and single boost by either the IM or ID route resulted in humoral and cellular immune responses that provided significant protection against disease and viremia. Although the ID route utilized one-fifth the DNA dose used in the IM route of vaccination, and the measured humoral and cellular immune responses trended lower, the level of protection was high and performed as well as the IM route for several clinical endpoints.

Needle-Free Devices and CpG-Adjuvanted DNA Improve Anti-HIV Antibody Responses of Both DNA and Modified Vaccinia Ankara-Vectored Candidate Vaccines

“…These results concur with other studies that have shown the immunogenicity of DNA vaccines to be enhanced with PharmaJet Stratis delivery as compared to needle and syringe [ 36 , 37 , 38 , 47 , 48 ]. This study also demonstrated significant improvement in the antibody responses with the MVA vaccine delivered using this device.…”

“…The needle-free jet injection developed by PharmaJet, Inc. can deliver vaccines using a narrow, precise fluid stream, which is an improvement over the standard needle and syringe [ 38 ]. The PharmaJet Stratis needle-free injection device improved immune responses to the DNA vaccine, with six of the ten rabbits having binding antibody responses after the second DNA vaccination, whereas none of the rabbits that received the DNA vaccines via needle injection developed binding antibody responses.…”

“…To further enhance this response, we investigated the impact of administering the DNA and MVA vaccines using two different strategies. In the first modification, we used the PharmaJet Stratis needle-free device, which has been used successfully to administer MVA vaccines against HIV [ 31 ] and smallpox [ 32 , 33 ] and inactivated influenza [ 34 ] and polio vaccines [ 35 ] and DNA vaccines against Zika [ 36 ], Hantavirus [ 37 ], and Venezuelan encephalitis virus [ 38 ]. Secondly, we assessed the addition of an adjuvant, which can enhance specific immune responses [ 39 , 40 ].…”

Improved DNA Vaccine Delivery with Needle-Free Injection Systems

“…Dr. Hooper’s group at USAMRIID tested their pWRG/VEE plasmid DNA vaccine in NHP delivered via Tropis ID or Stratis IM and compared immunogenicity and protection from viral challenge ( Table 3 ) [ 94 ]. Vaccinated animals showed significant protection from infection and although IM delivery induced more potent immune responses, animals in the ID group showed better protection from challenge.…”

A Historical Review of Military Medical Strategies for Fighting Infectious Diseases: From Battlefields to Global Health

“…A candidate vaccine is the V3526, even if it protects against only a few genotypes of VEEv [ 671 ]. For these reasons, the research has always continued over the years with a different approach, as DNA vaccines have proven particularly effective at eliciting protective immune responses in animal models [ 672 , 673 ]. Laboratory workers at USAMRIID are currently immunized with live (TC-83) and killed (C-84) vaccines.…”