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At least 541 records · Page 30Linked to original sources
PubMed2005

Progress in cytomegalovirus vaccine development.

Cytomegalovirus (CMV) causes considerable morbidity and disability in infants who acquire the infection in utero. Despite potent antiviral therapies, CMV also continues to be a major cause of disease in immunocompromised patients. Vaccines for CMV, therefore, could provide protection against CMV disease in an array of high-risk patient populations. Although the correlates of vaccine-engendered immunity that limit CMV disease are not fully understood, there has been significant progress in elucidating some of the key immunological correlates of protection. The optimal CMV vaccine strategy may depend on the patient population being targeted for protection. This review provides an update on CMV vaccines that are currently in preclinical and clinical development, and outlines important, as yet unanswered, questions about the nature of protective immune responses that will be required of potential CMV immunization strategies. Such questions must be answered before an optimal vaccine, and vaccine use strategy, can be implemented in clinical practice.

Cytomegalovirus↗
PubMed2005

Carbohydrate array analysis of anti-Tn antibodies and lectins reveals unexpected specificities: implications for diagnostic and vaccine development.

The Tn antigen is a carbohydrate antigen expressed in most carcinomas, during embryogenesis, on pathogenic parasites, and on HIV. It has been evaluated extensively as a potential diagnostic marker and several Tn-based vaccines are in clinical trials. Based on discrepancies in the literature regarding Tn expression, we began to question whether antibodies and lectins used routinely to detect the Tn antigen were providing accurate information. To investigate this possibility, a carbohydrate microarray and a highly sensitive assay were developed and three frequently used Tn receptors (HBTn1, Bric111, and VVL-B4) were evaluated. Carbohydrate-array analysis revealed unexpected cross-reactivity with other human carbohydrate epitopes. VVL-B4 bound the Tn antigen, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. Bric111 bound the Tn antigen, blood group A, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. HBTn1 showed the best selectivity, but still displayed moderate binding to blood group A. Implications for the development of Tn-based diagnostics and vaccines are discussed.

Antibodies↗
PubMed1989

Vaccine development. On relating immunology to the Third World: some studies on leprosy.

Leprosy is of interest to immunologists because the varied clinical manifestations of the disease correlate closely with the immunological spectrum. Resistance to infection is dependent on appropriate cell-mediated immunity, but patients with the lepromatous form fail to respond to antigens of M. leprae. In vitro studies have revealed the existence of T-suppressor cells of the phenotype CD8+, CD3+, HLA-DR+, FcR+, 9.3-, which are restricted by major histocompatibility complex (MHC) class II antigens. Several new candidate vaccines against leprosy have been effective in breaking immunological unresponsiveness and engendering cell-mediated immunity in lepromatous leprosy patients, including the combination of BCG+ killed M. leprae. Because BCG has unique adjuvant properties, we have begun to use molecular genetic approaches to develop BCG into a multivaccine vehicle capable of immunizing simultaneously against several pathogens. Both phage-based and plasmid-based strategies have been successfully developed for introducing selectable markers into BCG for the first time.

Bacterial Vaccines↗
PubMed1985

WHO's vaccine development programme.

The World Health Organization is playing a major international role in encouraging, coordinating, and where appropriate commissioning, research and development activities relevant to the control of high priority infectious diseases. The Expanded Programme on Immunization would be the vehicle for the introduction of new or improved vaccines. In many parts of the developing world the health infrastructure is strained to breaking point by the heavy load of disease. It has failed to make the best use of the already available technology. Immunization provides the simplest, least expensive and most effective intervention technology. Every effort is therefore needed to extend immunization coverage and lighten the burden on the health infrastructure and accelerate the overall development of the vast rural and peri-urban communities in the developing world. WHO has, on the one hand, to call on the most eminent scientists to give effective and simple interventions, and on the other, on the politicians, social leaders, economic managers, medical profession and all public health workers to build up the infrastructure to put intervention technologies into action.

Communicable Disease Control↗
PubMed2002

Exoerythrocytic malaria vaccine development: understanding host-parasite immunobiology underscores strategic success.

Malaria imposes an enormous health burden on people living in the tropics and effective control measures are urgently needed. The vast majority of deaths in humans from malaria are caused by one species of the protozoan, Plasmodium falciparum. An efficacious and cost-effective vaccine against this parasite is considered a holy grail of modern molecular medicine. A vaccine that targets liver-stage parasites would prevent infection from reaching the blood and causing clinical disease. Among around 40 known Plasmodium falciparum antigens, only a few are expressed exclusively by mosquito-transmitted sporozoites or infected hepatocytes. Studies in humans have consistently related immune responses to these antigens with resistance to infection or disease, providing a powerful rationale for the development of pre-erythrocytic vaccines. By dissecting the mechanism(s) of immunity to these antigens, we can best evaluate in different delivery systems epitopes associated with protection as components of a focused and coordinated multiantigen malaria vaccine strategy.

Animals↗
PubMed1996

Papillomavirus-like particles and HPV vaccine development.

Human papillomavirus-like particles (VLPs), self-assembled after high level expression of the papillomavirus L1 virion capsid protein in non-mammalian cells, are attractive candidates for a subunit vaccine to prevent genital HPV infection and the subsequent development of cervical cancer. In animal studies, purified VLPs induce high titers of antibodies against conformational type specific L1 epitopes. These antibodies neutralize homologous virions in in-vitro assays and protect against experimental challenge in several animal models. The encouraging results in animals justify the initiation of human trials of HPV VLP-based vaccines. Factors to be considered when designing these trials are discussed.

Animals↗
PubMed2002

Generation of a consensus sequence from prevalent and incident HIV-1 infections in West Africa to guide AIDS vaccine development.

We considered several key issues regarding the development of a DNA-based human immunodeficiency virus type 1 (HIV-1) vaccine: (1) should the candidate vaccine construct be derived from incident or prevalent HIV-1 strains; and (2) should circulating plasma virus, archived HIV-1 provirus recovered from peripheral blood mononuclear cells, or both be included? To address these questions, we collected circulating HIV-1 strains from infected individuals residing in Abidjan, Côte d'Ivoire. From a panel of 23 strains, 22 were HIV-1 subtype A in gag, 19 of which phylogenetically clustered with the recombinant HIV-1, CRF02-AG strains from West Africa. The mosaic genome of CRF02-AG was confirmed by sequencing the protease gene. A consensus gag p24 protein sequence was generated and 147 of 148 codons were identical to CRF02-AG (IbNG). Regardless of the sequence origin (RNA, provirus, incident, or prevalent), the gag p24 consensus sequences were highly representative of these distinct virologic compartments. These data suggest that the consensus sequence generated from incident and prevalent infections may provide an appropriate sequence for a DNA vaccine and is largely representative of the major circulating viral strain.

Africa, Western↗
PubMed1993

Scientific and social issues of human immunodeficiency virus vaccine development.

Development of a preventive immunogen for human immunodeficiency virus (HIV) infection is a national priority. The complexities associated with HIV host-virus interactions, coupled with the rapid progression of the HIV epidemic worldwide, have necessitated lowering expectations for an HIV vaccine that is 100 percent effective and have raised important scientific and nonscientific issues regarding development and use of preventive and therapeutic HIV vaccines.

AIDS Vaccines↗