Robert G. Brown

Long-lasting, single-dose immunocontraception of feral fallow deer in British Columbia

Practical field application of immunocontraception to manage overabundant deer has been hampered by the need for multiple inoculations to establish and maintain contraceptive antibody levels. To determine whether contraception lasting >1 year could be achieved with a single dose of SpayVac immunocontraceptive vaccine, we treated 41 female fallow deer (Dames dama) on James Island, British Columbia, Canada. Unlike other contraceptive vaccines, which use porcine zona pellucida (PZP) proteins and require boosters, SpayVac uses PZP encapsulated in liposomes and requires only 1 dose to achieve high antibody titers. Pregnancy status was determined for 22 treated does in 1, 2, or 3 breeding seasons (8-35 mo) post-immunization. No treated doe was pregnant, whereas 96.4% of untreated does were pregnant. High anti-PZP titers persisted throughout our study, suggesting that contraception will continue well beyond 3 years. The need for multiple inoculations with conventional PZP vaccines is a major limitation to their practicality for controlling fertility of free-ranging populations. The long-lasting, single-dose capability of SpayVac makes field applications more practical and less expensive while reducing treatment stress and risk of injury to deer.

Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®

BackgroundMelanoma tumors are known to express antigens that usually induce weak immune responses of short duration. Expression of both tumor-associated antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously targeting more than one antigen in a therapeutic vaccine. In this report, we show that VacciMax® (VM), a novel liposome-based vaccine delivery platform, can increase the immunogenicity of melanoma associated antigens, resulting in tumor elimination.MethodsC57BL/6 mice bearing B16-F10 melanoma tumors were vaccinated subcutaneously 6 days post tumor implantation with a mixture of synthetic peptides (modified p53: 232–240, TRP-2: 181–188 and PADRE) and CpG. Tumor growth was monitored and antigen-specific splenocyte responses were assayed by ELISPOT.ResultsVaccine formulated in VM increased the number of both TRP2- and p53-specific IFN-γ producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-γ producing splenocytes to one CTL epitopes (TRP2:180–188), suggesting that VM overcomes antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides formulated in VM successfully eradicated tumors in all mice. A control vaccine which contained all ingredients except liposomes resulted in eradication of tumors in no more than 20% of mice.ConclusionA single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors.

Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides

The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax®,VM) is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48–58 weeks old) bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-γ producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a) eradication of large tumors (> 700 mm3) b) in mice of advanced age c) in less than three weeks post-immunization d) following a single vaccination.

Improved Efficacy of a Licensed Acellular Pertussis Vaccine, Reformulated in an Adjuvant Emulsion of Liposomes in Oil, in a Murine Model

ABSTRACT The immunogenicities and efficacies of a licensed diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine and the same vaccine formulated in a liposome/oil emulsion adjuvant were compared in a mouse model of pertussis respiratory infection. A single dose of the liposome/oil emulsion-adjuvanted vaccine produced significantly higher antibody levels than one dose of the licensed vaccine and protected mice from Bordetella pertussis infection with an efficacy equivalent to that of three doses of the licensed vaccine.

Efficacy of SpayVac® is excellent: a comment on Gray et al. (2010)

In reporting the results of a trial of contraceptive vaccines in wild horses, Gray et al. (2010) misidentified one of the vaccines as SpayVac®, a porcine zona pellucida (pZP) vaccine that owes its typically very high efficacy to a special DepoVax® liposome technology. We believe that the absence of DepoVax® liposomes ought to have been considered as a possible explanation for the unexpectedly low efficacy that was observed.