A Vaccine for Gonorrhea

P. Frederick Sparling, Christopher E. Thomas and Weiyan Zhu

There is minimal evidence for naturally-acquired immunity to reinfection by the gonococcus. However, recent improvements in understanding the roles in pathogenesis played by a variety of cell surface molecules, availability of multiple models for infection including human volunteers, and developm...

A Vaccine for Nontypable Haemophilus influenzae

Allan W. Cripps and Jennelle M. Kyd

Nontypable H. influenzae (NTHI) is a common commensal of the upper respiratory tract residing in both the nasopharynx and the posterior oropharynx. It is one of the leading causative bacterial pathogens of otitis media (OM) in children and serious urogenital, neonatal and mother-infant infections...

Academic Pursuits of Vaccines against Group B Streptococcus

Lawrence C. Paoletti

Today’s welcome declines in the prevalence of early-onset group B Streptococcus (GBS) neonatal disease—due to active surveillance and use of intrapartum antibiotic prophylaxis 1—may become tomorrow’s problematic emergence of GBS strains bearing antibiotic resistance.2,3 Vaccines against GBS offer...

Activation of the Innate Immune System by DNA Vaccines

Julie Fitzgerald and Hildegund C. J. Ertl

DNAvaccines were discovered serendipitously by gene therapists attempting to replace missing or faulty genes with bacterial expression vectors. The transgene product was found to elicit an immune response that rapidly eliminated the transduced cells¹ reducing the attractive...

Anti-Tumor Immunotherapy with Synthetic Peptides Representing Tumor-Associated T-Cell Epitopes: Implications for Peptide-Based Vaccination of Cervical Cancer

Maaike E. Ressing, René E.M. Toes, Stephen P. Schoenberger, Remco M.P. Brandt, Joan H. de Jong, W. Martin Kast, Rienk Offringa and Cornelis J.M. Melief

Alternative approaches for the prevention or treatment of cancer are now emerging. The goal of new treatment modalities is to combine effective anti-tumor activity with a reduction of the side effects to healthy tissues, still constituting a severe complication of conventional cancer therapy (i.e...

Biological Aspects and Prospects for Adjuvants and Delivery Systems

Bror Morein and Ke-Fei Hu

There is no all-encompassing definition for an adjuvant, but an old definition is: a substance that enhances the immunogenicity of coadministered antigens without !=inducing an immune response to itself. Allison and Byars¹ introduced functional structures into the terminology ...

Cancer Peptide Vaccines in Clinical Trials

Jeffrey S. Weber

The revelation that protein antigens were processed into peptides by a pathway of intracellular degradation and presented on the surface of antigen presenting cells for recognition by T-cells in association with class I and II MHC molecules created a new paradigm for the generation and detection ...

Carcinoembryonic Antigen (CEA) Peptides and Vaccines for Carcinoma

Jeffrey Schlom

This Chapter addresses the current status of the development of recombinant vaccines employing carcinoembryonic antigen (CEA) as the target antigen. Included is an over view of preclinical studies and the pros and cons of CEA as a vaccine target. Several CEA peptides that are recognized by human ...

Chemokines: Role as Immunomodulators and Potential as Adjuvants for DNA Vaccines

Philip M. Murphy

Adaptive immune responses require proper positioning of antigenpresenting cells (APCs) and antigenspecific lymphocytes in specific microdomains of secondary lymphoid tissue. This process is guided in part by members of the chemokine family of leukocyte chemoattractants. In addition, chem...

Chlamydia trachomatis and Chlamydia pneumoniae Vaccines

Svend Birkelund and Gunna Christiansen

Chlamydia spp. are obligate intracellular Gram negative bacteria with a unique biphasic developmental cycle. C. trachomatis and C. pneumoniae most frequently cause human infections. C. trachomatis strains of the trachoma biovar (serovar A, B and C) are mucosal pathogens that cause the ocular infe...

Clinical Issues for New Vaccine Technologies

Luc Hessel

Vaccination as a means of preventing infectious diseases arguably has had the greatest impact on human health of any medical intervention.¹ Since the pioneer work of Jenner and Pasteur, the development of vaccines has been the consequence of the uninterrupted introduction o...

Clinical Trials of HER-2/neu Peptide-Based Vaccines

Mary L. Disis and Martin A. Cheever

Cancer vaccines are not used routinely in the clinical practice of most oncologists, despite decades of study. Several advances in basic immunology over the last few years have forced a re-evaluation of cancer vaccine development. The most important finding has been that human tumors are immunoge...

Critical Dependence of the Peptide Delivery Method on the Efficacy of Epitope Focused Immunotherapy

Gregory E. Holt, Markwin P. Velders, Michael P. Rudolf, Laurie A. Small, Maurizio Provenzano, Sanne Weijzen, Diane M. Da Silva, Marten Visser, Simone A.J. ter Horst, Remco M.P. Brandt and W. Martin Kast

Tumor immunotherapy describes the use of the immune system as a tool to eliminate cancer from the stricken patient. The theory contends that immunization against certain proteins either associated with or specific for the tumor will create a potent cytotoxic T lymphocyte (CTL) immunity able to se...

Cytokines and Immunomodulatory Ligands as Genetic Adjuvants

Hildegund C. J. Ertl

Genetic adjuvant is a term for vaccine ingredients composed of expression vectors encoding biologically active molecules such as cytokines, chemokines (detailed in Chapter 15), soluble forms of cell ligands, adhesion proteins, or other immuno-reactive molecules. These vectors added to...

Cytotoxic T Cell Epitopes and Tissue Distribution of the HER-2/neu Proto-Oncogene: Implications for Vaccine Development

Barbara Seliger, Koji Kono, Y. Rongcun and Rolf Kiessling

The development of immunotherapeutic methods to treat cancer is critically depen dent on the identification of tumor-associated antigens (TAA). Several immunodominant peptide epitopes, recognized by cytotoxic T-lymphocytes (CTL) lines and clones, have been defined from human melanomas.1-6 This wa...

Dendritic Cells: Important Adjuvants During DNA Vaccinati

Ralph M. Steinman, Constantin Bona and Kayo Inaba

Vaccine design focuses on the identification of safe forms of antigen that elicit protective immunity. Adjuvants are also critical for efficacy, especially for inducing strong T cell‑mediated responses. Dendritic cells (DCs) are natureís adjuvants, specialized to capture and pro...

DNA Delivery With Attenuated Intracellular Bacteria

Joachim Fensterle and Stefan H.E. Kaufmann

For centuries, intracellular bacteria have been a major cause of death globally. Notably, Mycobacterium tuberculosis killed more than 2 million individuals in 1999 worldwide, a number which was only exceeded by HIV.¹

Intracellular bacteria are defined ...

DNA Vaccines

Daniel E. McCallus, Catherine J. Pachuk, Shaw-guang Lee and C. Satishchandran

Research into the use of DNA vaccines has shown that this mode of immunization has much potential for widescale application. The ability to elicit an immune response by injection of DNA encoding the gene for the protein-antigen of interest has been demonstrated by a variety of methods...

DNA Vaccines

John J. Donnelly

DNA vaccines have been used widely in laboratory animals and nonhuman primates over the last decade to induce antibody and cellular immune responses. This approach has shown some promise in models of infectious diseases of both bacterial and viral origin as well as in tumor models. Clinical trial...

DNA Vaccines Against Bacterial Pathogens

M.A. Chambers, H.M.Vordermeier, R.G. Hewinson and D.B. Lowrie

Bacterial pathogens against which DNA vaccines are being developed encompass both intracellular and extra-cellular pathogens as well as vaccines against bacterial toxins. DNA vaccination has an inherent bias towards generating cellular immunity by virtue of the intracellular origin of th...

DNA Vaccines Against Herpesviruses

Christopher Pack and Barry T. Rouse

Herpesviruses are significant pathogens of mankind, and vaccines of proven efficacy remain unavailable. This review briefly examines the current state of vaccinology against herpesviruses and then discusses experiments in animal model systems that have evaluated DNA vaccines as a means o...

DNA Vaccines Against RNA Viruses

Jeffrey B. Ulmer

DNA vaccines have been used successfully in many animal models of infectious and non‑infectious diseases. The former has included viruses, bacteria, parasites, and other pathogens. However, because virus proteins are expressed by infected cells of the host, DNA vaccines may, in pri...

DNA Vaccines as Cancer Treatment Modalities

Ronald C. Kennedy, Michael H. Shearer and Robert K. Bright

Therapeutic vaccination has recently regained its optimism as a potential immunologic based modality for the treatment of cancer patients. Cancer vaccine based clinical trials are being initiated at a rapid pace, yet work still must be performed to determine the best formulation of the v...

DNA Vaccines for Allergic Diseases

Kaw Yan Chua, Betina Wolfowicz and Patrick G. Holt

DNA vaccines have prevented anaphylaxis in several models of murine allergy. The mechanisms of prevention are still unclear. In this chapter we describe different immunization protocols with a focus on those that may have induced immunoregulation. This analysis will unravel some of the e...

DNA Vaccines for Papillomavirus Infections

Sancy A. Leachman and Janet L. Brandsma

The major advances in approaches in vaccinology can be subdivided into three “waves”, each resulting from breakthrough technologies. The initial wave employed newly developed cell culture methods to produce attenuated live viruses and killed viruses for use as vaccines. The next wave began with t...