Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in rabbits

Brandsma, Janet L.; Shlyankevich, Mark; Buonocore, Linda; Roberts, Anjeanette; Becker, Steven M.; Rose, John K.

doi:10.1016/j.vaccine.2006.08.012

Cited by 17 publications

(28 citation statements)

References 42 publications

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“…We recently demonstrated the ability of VSV-based vaccination to induce immunotherapeutic responses in the CRPVrabbit model. That study showed that VSV-based vaccines expressing the CRPV E6 protein significantly reduced papilloma growth and eradicated all papillomas in some rabbits (3). The present study extends those findings.…”

supporting

confidence: 88%

“…In the present study, VSV-based vectors individually expressing the CRPV E1, E2, and E7 proteins were generated and compared to a previously generated VSV-E6 vaccine (3) for therapeutic efficacy against CRPV-induced rabbit papillomas. Because multicomponent vaccines may elicit broader arrays of immune responses than individual vaccines, they may increase vaccine efficacy, especially among genetically heterogeneous populations such as rabbits and humans.…”

mentioning

confidence: 99%

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Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus

Brandsma

Shylankevich²,

et al. 2007

J Virol

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Persistent human papillomavirus (HPV)-associated benign and malignant lesions are a major cause of morbidity and mortality worldwide. Vaccination against HPV early proteins could provide an effective means of treating individuals with established infections. Recombinant vesicular stomatitis virus (VSV) vectors have been used previously to elicit strong humoral and cellular immune responses and develop prophylactic vaccines. We have shown that VSV vectors also can be used to elicit therapeutic immunity in the cottontail rabbit papillomavirus (CRPV)-rabbit model of high-risk HPV infection. In the present study, three new VSV vectors expressing the CRPV E1, E2, or E7 protein were produced and compared to the previously generated VSV-E6 vector for therapeutic efficacy. To determine whether vaccine efficacy could be augmented by simultaneous vaccination against two CRPV proteins, the four vaccines were delivered individually and in all possible pairings to rabbits 1 week after CRPV infection. Control rabbits received the recombinant wild-type VSV vector or medium only. Cumulative papilloma volumes were computed for analysis of the data. The analyses showed that VSV-based vaccination against the E1, E2, E6, or E7 protein significantly reduced papilloma volumes relative to those of the controls. Furthermore, VSV-based CRPV vaccination cured all of the papillomas in 5 of 30 rabbits. Of the individual vaccines, VSV-E7 was the most effective. The VSV-E7 vaccine alone was the most effective, as it reduced cumulative papilloma volumes by 96.9% overall, relative to those of the controls, and ultimately eliminated all of the disease in all of the vaccinees. Vaccine pairing was not, however, found to be beneficial, suggesting antigenic competition between the coexpressed CRPV proteins. These preclinical results, obtained in a physiologically relevant animal model of HPV infection, demonstrate that VSV vectors deserve serious consideration for further development as therapeutic antitumor vaccines.Human papillomavirus (HPV) infections induce benign proliferative epithelial lesions (papillomas) at cutaneous and mucosal sites. Persistent lesions cause widespread morbidity and, when they progress to cancer, mortality (reviewed in references 1, 2, 7, 13, and 23). The new HPV virus-like particle (VLP) vaccine elicits strong HPV type-specific neutralizing antibodies and protects against subsequent infection with the corresponding HPV types (12). However, since it is unlikely to be immunotherapeutic, additional HPV vaccines are needed to ameliorate the severity of disease in the millions of people already infected with HPV (reviewed in reference 37).A promising new approach to vaccine development uses attenuated recombinant vesicular stomatitis viruses (VSVs) as vaccines (reviewed in reference 26). Compared to other viral vectors, the VSV vector offers several advantages. It is replication competent, like the most effective human vaccines, but is not a human pathogen. It induces strong cell-mediated and humoral immune responses compara...

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confidence: 88%

mentioning

confidence: 99%

Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus

Brandsma

Shylankevich²,

et al. 2007

J Virol

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“…DNA vectors can be particularly useful priming agents for other vaccines based on viral vectors [24]. Future studies will assess the ability of CRPV early gene DNA vaccines to augment therapeutic immune responses induced by recombinant adenoviruses [25] and vesicular stomatitis viruses (VSVs) [10,11] encoding the same protein (s). Papilloma growth in rabbits vaccinated after papilloma formation.…”

Section: Discussionmentioning

confidence: 99%

“…Six rabbits were infected with CRPV and 22 days later allocated to two groups to achieve equivalent papilloma frequencies and volumes in each group, as previously described [11]. At that time, there were no significant differences between the groups with respect to either papilloma frequency or papilloma volume, as shown in Table 2.…”

Section: Effects Of Ube1267 Dna Vaccination In Rabbits Bearing Papillmentioning

confidence: 99%

Therapeutic vaccination of rabbits with a ubiquitin-fused papillomavirus E1, E2, E6 and E7 DNA vaccine

Brandsma

Shlyankevich

Zelterman

et al. 2007

Vaccine

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Previously we showed that intracutaneous vaccination of rabbits with DNA vectors encoding ubiquitin-fused versions of the cottontail rabbit papillomavirus (CRPV) early proteins E1, E2, E6 and E7 protected against subsequent challenge with CRPV. Here we tested the immunotherapeutic activity of a vaccine composed of the four CRPV DNA vectors (designated UbE1267) in rabbits. The results show that the UbE1267 DNA vaccine, relative to empty vector DNA, virtually eliminated papilloma growth in rabbits with subclinical infection and greatly reduced papilloma volumes in rabbits bearing papillomas at the time of vaccination. These results in a physiologically relevant animal model of high-risk human papillomavirus (HPV) infection indicate that DNA vaccines targeting the early papillomavirus proteins may have a role in the treatment of HPV-associated lesions in humans.

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“…Taking a more biologically relevant approach, others have built VSVs that express viral genes from known carcinogens, for the treatment of virus-infected tumors. For example, intradermal vaccination with VSV-expressing cottontail rabbit papillomavirus (CRPV) proteins was shown to induce complete regression of CRPV-induced papillomas in rabbits (40)(41)(42), and similar observations were made in murine papilloma models (43). However, as most tumors lack strong viral antigens, this approach, while having the potential to treat a small subset of human cancers, does not have broad therapeutic use.…”

Section: Engineering Oncolytic Vaccines To Prime or Boost Antitumor Imentioning

confidence: 97%

Molecular Pathways: Multimodal Cancer-Killing Mechanisms Employed by Oncolytic Vesiculoviruses

Mahoney

Stojdl

2013

Clinical Cancer Research

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Cancer is a heterogeneous disease that, for the most part, is not effectively managed with existing therapies. Oncolytic viruses are an attractive class of experimental cancer medicine because, unlike conventional chemotherapeutic and molecularly targeted drugs, they orchestrate tumor cell death in multiple ways simultaneously. In this review, we discuss the numerous cancer-killing "pathways" marshalled by oncolytic vesiculoviruses. From directly infecting and lysing malignant cells, to engaging the host's innate and adaptive anticancer immune responses, to inducing vascular collapse within a tumor, oncolytic vesiculovirus therapy commandeers a coordinated, multipronged assault on cancer that is curative in numerous preclinical models. And as our appreciation of these mechanisms has progressed, so has our capacity to engineer improved outcomes. Notably, efforts to polarize the host's immune system toward the tumor and away from the virus have been particularly effective in immunocompetent murine models, and hold tremendous therapeutic promise for human patients. With a first-in-man phase I trial recently initiated in the United States, the clinical significance of oncolytic vesiculorivus therapy, after nearly 15 years of development, may soon come into focus.

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Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in rabbits

Cited by 17 publications

References 42 publications

Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus

Vesicular Stomatitis Virus-Based Therapeutic Vaccination Targeted to the E1, E2, E6, and E7 Proteins of Cottontail Rabbit Papillomavirus

Therapeutic vaccination of rabbits with a ubiquitin-fused papillomavirus E1, E2, E6 and E7 DNA vaccine

Molecular Pathways: Multimodal Cancer-Killing Mechanisms Employed by Oncolytic Vesiculoviruses

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