Listeria monocytogenesDelivery of HPV-16 Major Capsid Protein L1 Induces Systemic and Mucosal Cell-Mediated CD4+and CD8+T-Cell Responses After Oral Immunization

Mustafa, Waleed; Maciag, Paulo; Pan, Zhen-Kun; Weaver, Jessica L.; Xiao, Yuhong; Isaacs, Stuart N.; Paterson, Yvonne

doi:10.1089/vim.2008.0071

Cited by 20 publications

(7 citation statements)

References 52 publications

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“…Here we show that CD4+ T cell help plays an important role in the enhancement of antigen-specific CD8+ T cell immune responses observed in our vaccination regimen as co-administration with the reverse sequence of BPV1 L1 or L2 did not enhance the antigen-specific CD8+ T cell responses. Studies have shown that L1 and L2 are generally much more effective in eliciting CD4+ T cell responses [14][15][16][17][18]. While it is possible that BPV L1 or L2 could elicit some CD8+ T cell responses, we Fig.…”

Section: Discussionmentioning

confidence: 69%

“…In the current study, we aim to combine intracellular targeting strategies using CRT with a strategy to enhance CD4 + T help for the development of a therapeutic HPV DNA vaccine. Since papillomavirus L1 or L2 antigens likely contain CD4 + T cell epitopes [14][15][16][17][18], we reasoned that co-administration of vectors containing codon-optimized bovine papillomavirus (BPV) L1 and L2 may provide CD4 + T cell help and enhance the antigenspecific CD8 + T cell immune responses generated by DNA vaccines. An additional potential benefit would be the induction of neutralizing antibody and protective immunity [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination

Yang

Peng

et al. 2015

Cell Biosci

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BackgroundDNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8+ T cell immune responses and antitumor effects against E7-expressing tumors. In the current study, we aim to introduce an approach to elicit potent CD4+ T cell help for the enhancement of antigen-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2.ResultWe showed that co-administration of vectors containing codon-optimized bovine papillomavirus type 1 (BPV-1) L1 and L2 in combination with DNA vaccines could elicit enhanced antigen-specific CD8+ in both CRT/E7 and ovalbumin (OVA) antigenic systems. We also demonstrated that co-administration of vectors expressing BPV-1 L1 and/or L2 DNA with CRT/E7 DNA led to the generation of L1/L2-specific CD4+ T cell immune responses and L1-specific neutralizing antibodies. Furthermore, we showed that co-administration with DNA encoding BPV1 L1 significantly enhances the therapeutic antitumor effects generated by CRT/E7 DNA vaccination. In addition, the observed enhancement of CD8+ T cell immune responses by DNA encoding L1 and L2 was also found to extend to HPV-16 L1/L2 system.ConclusionOur strategy elicits both potent neutralizing antibody and therapeutic responses and may potentially be extended to other antigenic systems beyond papillomavirus for the control of infection and/or cancer.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination

Yang

Peng

et al. 2015

Cell Biosci

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“…L. monocytogenes antigen processing and presentation via the major histocompatability complex class I pathway makes it an attractive vector for delivery of viral and cancer antigens. Animal studies show that L. monocytogenes vectors can generate T cell‐mediated immune responses to lymphocytic choriomeningitis virus, influenza virus, HIV‐1 Gag, and human papilloma virus‐16 antigens (1–5). Despite these promising results, there are safety concerns related to using recombinant wild type L. monocytogenes as a vaccine vector due to the high degree of morbidity and mortality that results from naturally acquired infection.…”

mentioning

confidence: 99%

Attenuated Listeria monocytogenes vaccine vectors expressing Influenza A nucleoprotein: preclinical evaluation and oral inoculation of volunteers

Johnson

Blair

Zeller

et al. 2011

Microbiology and Immunology

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Listeria monocytogenes vectors have shown promise for delivery of viral and tumor antigens in animals. We used two mutant vector strains deleted for actA/plcB (BMB72) and actA/inlB (BMB54), and engineered both strains to secrete a heterologous nucleoprotein antigen from the Influenza A virus. Strains were evaluated in vitro and in mice. Twenty-two healthy volunteers received single oral doses of either strain in a physiological study of safety, shedding, and immunogenicity. Volunteers were observed in the hospital for seven days and had daily blood cultures, routine safety blood tests (complete blood count with differential; hepatic and renal function), and fecal cultures; none had fever, positive blood cultures, prolonged shedding, or serious or unexpected events. Live attenuated bacteria expressing foreign antigens present a promising approach in the development of human immunotherapies and vaccines. Favorable attributes of Listeria monocytogenes include its innate immunostimulatory properties, efficient cytosolic entry of antigen presenting cells, and its ability to stimulate vigorous CD4 and CD8 T cell responses. L. monocytogenes antigen processing †Present address:

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“…Simply, L. monocytogenes stimulates antigen-specific CD8+ and CD4+ T cell responses following its evasion of immune destruction by releasing Lm toxin to avoid phagosomal lysis. However, the most appealing factor of the L. monocytogenes vector is that the immune response can be easily controlled by antibiotics should the body react adversely to Lm [101][102][103][104]. With regards to viral vectors, a few viruses, such as the vaccinia virus, adenovirus, vesicular stomatitis virus, and alphavirus, have distinguished themselves and show great promise.…”

Section: Molecular Therapies In Developmentmentioning

confidence: 99%

Modern Molecular and Clinical Approaches to Eradicate HPVMediated Cervical Cancer

Evans¹,

Filippova²,

Swensen³

et al. 2013

Human Papillomavirus and Related Diseases From Bench to Bedside a Diagnostic and Preventive Perspective

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Additional information is available at the end of the chapter http://dx.doi.org/10.5772/55810 . IntroductionCervical cancer was formerly the second most common cancer killer of women worldwide. Following widespread adoption of Papanicolau cytologic screening Pap test for cervical cancer in the s, this began to change. Today, advanced cervical cancer is rare in screened populations. Although an uncommon disease in developed nations, internationally about , women annually are diagnosed with cervical cancer, and about half of those women will die of their disease. In global terms, this ranks second only to breast cancer as a cause of cancer-specific mortality. Over the past three decades the scientific community has witnessed spectacular advances in the understanding of the underlying pathophysiology of cervical cancer, with the most profound discovery being in of the identification of the human papillomavirus HPV within cervical cancer a discovery that earned Harold Zur-Hausen, M.D the Nobel prize for Medicine and Physiology in . A viral etiology for cervical cancer implied that it may be possible to eradicate cervical cancer through vaccination. This promise was partially fulfilled in when the United States Food and Drug Administration approved an HPV vaccine for the prevention of HPV-induced cervical dysplasia and/or cancer. These advances, profound though they are, have yet to eradicate cervical cancer. Furthermore, due to the pervasiveness of HPV infection and the timeline of disease progression, it will be a few decades before we will be able to determine the impact preventive practices are having on cancer incidence and prevalence. In addition, those for whom preventative measures are not a solution, including HIV + individuals as well as women already infected with HR-HPV, await an answer.Over the past several years, developments in innovative imaging, superior surgical technologies, immunotherapies, and molecular therapies have surfaced, making the eradication of cervical cancer a much more achievable goal than in the past. Several areas of cervical cancer research continue to address the challenges posed by the need for appropriate therapeutic alternatives, and progress is occurring at each level of clinical management ranging from detection to the development of small molecule antiviral leads. Because the field is evolving rapidly in all directions and related disciplines, it is helpful to summarize the status of our growth, and to recognize those pioneering efforts that may ultimately contribute to achieving our goal of eliminating cervical cancer. This review seeks to survey the current understanding of cervical cancer etiology and treatment and to review areas requiring additional progress. . Prevention, interception and early detectionDisease Burden and Risk: Approximately million Americans are currently infected with HPV, and another million new infections occur annually. In about percent of these cases, the infection is cleared by the immune system within two years [ , ]. However, a relatively smal...

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Listeria monocytogenesDelivery of HPV-16 Major Capsid Protein L1 Induces Systemic and Mucosal Cell-Mediated CD4⁺and CD8⁺T-Cell Responses After Oral Immunization

Cited by 20 publications

References 52 publications

Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination

Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination

Attenuated Listeria monocytogenes vaccine vectors expressing Influenza A nucleoprotein: preclinical evaluation and oral inoculation of volunteers

Modern Molecular and Clinical Approaches to Eradicate HPVMediated Cervical Cancer

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