Search

The HIV Vaccine Trials Network (HVTN) 087 vaccine trial assessed the effect of increasing doses of pIL-12 (interleukin-12 delivered as plasmid DNA) adjuvant on the immunogenicity of an HIV-1 multiantigen (MAG) DNA vaccine delivered by electroporation and boosted with a vaccine comprising an attenuated vesicular stomatitis virus expressing HIV-1 Gag (VSV-Gag). We randomized 100 healthy adults to receive placebo or 3 mg HIV-MAG DNA vaccine (ProfectusVax HIV-1 gag / pol or ProfectusVax nef / tat / vif , env ) coadministered with pIL-12 at 0, 250, 1,000, or 1,500 μg intramuscularly by electroporation at 0, 1, and 3 months followed by intramuscular inoculation with 3.4 × 10 7 PFU VSV-Gag vaccine at 6 months. Immune responses were assessed after the prime and boost and 6 months after the last vaccination. High-dose pIL-12 increased the magnitude of CD8 + T-cell responses postboost compared to no pIL-12 ( P = 0.02), while CD4 + T-cell responses after the prime were higher in the absence of pIL-12 than with low- and medium-dose pIL-12 ( P ≤ 0.05). The VSV boost increased Gag-specific CD4 + and CD8 + T-cell responses in all groups ( P < 0.001 for CD4 + T cells), inducing a median of four Gag epitopes in responders. Six to 9 months after the boost, responses decreased in magnitude, but CD8 + T-cell response rates were maintained. The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in the HVTN 090 trial, leading to broad epitope targeting and maintained CD8 + T-cell response rates at early memory. The addition of high-dose pIL-12 given with a DNA prime by electroporation and boosted with VSV-Gag increased the CD8 + T-cell responses but decreased the CD4 + responses. This approach may be advantageous in reshaping the T-cell responses to a variety of chronic infections or tumors. (This study has been registered at ClinicalTrials.gov under registration no. NCT01578889.)., (Copyright © 2017 American Society for Microbiology.)

Plasmodium falciparum sexual stage surface antigen Pfs25 is a well-established candidate for malaria transmission-blocking vaccine development. Immunization with DNA vaccines encoding Pfs25 has been shown to elicit potent antibody responses in mice and nonhuman primates. Studies aimed at further optimization have revealed improved immunogenicity through the application of in vivo electroporation and by using a heterologous prime-boost approach. The goal of the studies reported here was to systematically evaluate the impact of codon optimization, in vivo electroporation, and N-linked glycosylation on the immunogenicity of Pfs25 encoded by DNA vaccines. The results from this study demonstrate that while codon optimization and in vivo electroporation greatly improved functional immunogenicity of Pfs25 DNA vaccines, the presence or absence of N-linked glycosylation did not significantly impact vaccine efficacy. These findings suggest that N-glycosylation of Pfs25 encoded by DNA vaccines is not detrimental to overall transmission-blocking efficacy., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Protection against the avian influenza (AI) H5N1 virus is suspected to be mainly conferred by the presence of antibodies directed against the hemagglutinin (HA) protein of the virus. A single electroporation delivery of 100 or 250 μg of a DNA vaccine construct, pCAG-HA, carrying the HA gene of strain A/Hanoi/30408/2005 (H5N1), in chickens led to the development of anti-HA antibody response in 16 of 17 immunized birds, as measured by a hemagglutination inhibition (HI) test, competitive enzyme-linked immunosorbent assay (cELISA), and an indirect ELISA. Birds vaccinated by electroporation (n = 11) were protected from experimental AI challenge with strain A/chicken/Pennsylvania/1370/1/1983 (H5N2) as judged by low viral load, absence of clinical symptoms, and absence of mortality (n = 11). In contrast, only two out of 10 birds vaccinated with the same vaccine dose (100 or 250 μg) but without electroporation developed antibodies. These birds showed high viral loads and significant morbidity and mortality after the challenge. Seroconversion was reduced in birds electroporated with a low vaccine dose (10 μg), but the antibody-positive birds were protected against virus challenge. Nonelectroporation delivery of a low-dose vaccine did not result in seroconversion, and the birds were as susceptible as those in the control groups that received the control pCAG vector. Electroporation delivery of the DNA vaccine led to enhanced antibody responses and to protection against the AI virus challenge. The HI test, cELISA, or indirect ELISA for anti-H5 antibodies might serve as a good predictor of the potency and efficacy of a DNA immunization strategy against AI in chickens.

Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

Administration of a clade C/B' candidate HIV-1 DNA vaccine, ADVAX, by in vivo electroporation (EP) was safe and more immunogenic than intramuscular administration without EP. The breadth and specificity of T-cell responses to full-length Env were mapped. Responses to multiple Env regions were induced, with most focusing on V3/C4 and V2 regions, including the α4β7 integrin-binding domain. The breadth of responses induced by this DNA vaccine regimen was comparable to that of viral-vectored vaccine regimens.

We evaluated the immunogenicity and protective efficacy of a DNA vaccine expressing codon-optimized envelope glycoprotein genes of Venezuelan equine encephalitis virus (VEEV) when delivered by intramuscular electroporation. Mice vaccinated with the DNA vaccine developed robust VEEV-neutralizing antibody responses that were comparable to those observed after administration of the live-attenuated VEEV vaccine TC-83 and were completely protected from a lethal aerosol VEEV challenge. The DNA vaccine also elicited strong neutralizing antibody responses in rabbits that persisted at high levels for at least 6 months and could be boosted by a single additional electroporation administration of the DNA performed approximately 6 months after the initial vaccinations. Cynomolgus macaques that received the vaccine by intramuscular electroporation developed substantial neutralizing antibody responses and after an aerosol challenge had no detectable serum viremia and had reduced febrile reactions, lymphopenia, and clinical signs of disease compared to those of negative-control macaques. Taken together, our results demonstrate that this DNA vaccine provides a potent means of protecting against VEEV infections and represents an attractive candidate for further development.