DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant

Abstract

The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.

Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice

“…In our previous work, based on a consensus sequence of the ectodomain of E protein (cE80) of the four DENV serotypes , heterologous (DNA prime-protein boost) regimens elicited greater systemic immune response and more effective tetravalent protection than did homologous DNA immunization. As the optimal immunization regimen, DNA vaccination followed by protein boosting has been applied to a variety of infectious agents to improve the immunogenicity and protective efficacy of vaccines (Menon et al, 2017;Wang et al, 2017;Cai et al, 2018). Further investigation should be performed to assess whether it is an appropriate strategy for our dengue DNA vaccine candidate.…”

Tilapia Lake Virus Vaccine Development: A Review on the Recent Advances

“…Moreover, their safety of administration (no possibility of reversion to a pathogenic state) and fast-track design make them ideal vaccine platforms that can be deployed rapidly and easily in the case of disease outbreaks [ 35 ]. Nucleic acid vaccines have also been demonstrated to be potent inducers of both humoral and cellular adaptive immune responses [ 67 , 68 ], and although the use of DNA or mRNA as the genetic material dictates the production pipeline, the stability, and the storage conditions of these vaccines, their production remains relatively simple, flexible, and scalable.…”

“…Other injection delivery routes such as particle-mediated epidermal delivery by gene gun has been documented for some DNA vaccines, in which DNA vaccines are coated with small gold particles and delivered intradermally by air-pressure [ 67 ]. Although this novel technology has been proven effective in fish [ 121 , 122 ], it remains too expensive and thus not cost effective for commercial aquaculture.…”