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Results for “Vaccine Development”

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At least 253 records · Page 14Linked to original sources

PubMed1991

Construction of plasmid vectors with a non-antibiotic selection system based on the Escherichia coli thyA+ gene: application to cholera vaccine development.

The construction of live oral carriers based on attenuated Salmonella strains as vectors offers a new approach to vaccine development. We have constructed a set of plasmid vectors which have the thyA gene of Escherichia coli (encoding thymidylate synthetase) as the marker for selection and maintenance of plasmid clones. The thyA system offers an alternative to antibiotic-resistance selection markers. It can be easily adapted to a particular host-vector combination since thyA chromosomal mutations can be readily introduced by trimethoprim selection. We also describe the construction of thyA-based plasmids with the Vibrio cholerae rfb genes (encoding O-antigen biosynthesis of the Inaba serotype). These have been found to be useful in the construction of candidate bivalent cholera-typhoid vaccines.

Antigens, Bacterial↗

PubMed2025

Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.

Tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, increasingly complicated by the emergence of drug-resistant strains and limitations in existing diagnostic and therapeutic strategies. Despite decades of global efforts, the disease continues to impose a significant burden, particularly in low- and middle-income countries (LMICs) where health system weaknesses hinder progress. This comprehensive review explores recent advancements in TB diagnostics, antimicrobial resistance (AMR surveillance), treatment strategies, and vaccine development. It critically evaluates cutting-edge technologies including CRISPR-based diagnostics, whole-genome sequencing, and digital adherence tools, alongside therapeutic innovations such as shorter multidrug-resistant TB regimens and host-directed therapies. Special emphasis is placed on the translational gap-highlighting barriers to real-world implementation such as cost, infrastructure, and policy fragmentation. While innovations like the Xpert MTB/RIF Ultra, BPaLM regimen, and next-generation vaccines such as M72/AS01E represent pivotal progress, their deployment remains uneven. Implementation science, cost-effectiveness analyses, and health equity considerations are vital to scaling up these tools. Moreover, the expansion of the TB vaccine pipeline and integration of AI in diagnostics signal a transformative period in TB control. Eliminating TB demands more than biomedical breakthroughs-it requires a unified strategy that aligns innovation with access, equity, and sustainability. By bridging science with implementation, and integrating diagnostics, treatment, and prevention within robust health systems, the global community can accelerate the path toward ending TB.

diagnostic innovation↗

PubMed2000

The potential for vaccine development against chlamydial infection and disease.

Chlamydia trachomatis and Chlamydia pneumoniae appear to share a common immunobiology with about 80% of their protein coding genes being orthologs. Progress in DNA vaccine development for C. trachomatis suggests that such a subunit approach may prove useful for C. pneumoniae. The recent finding that it is possible to select for chlamydiae with targeted mutations in key metabolic genes together with the new knowledge of the chlamydia genome also suggests that it may be possible to develop live attenuated strains of chlamydiae for use as vaccine.

Animals↗

PubMed2003

[Status and current strategies of HIV vaccine development].

Despite intensive research efforts a vaccine against HIV has not yet been developed twenty years even after the onset of the HIV-epidemic. The problems in the development of an HIV-vaccine as well as former and current strategies to overcome these problems are presented here. The current status of human studies of different candidate vaccines is outlined.

AIDS Vaccines↗

PubMed2005

Structural and functional characterisation of the Toll like receptor 9 of Aotus nancymaae, a non-human primate model for malaria vaccine development.

In the absence of suitable rodent animal models for Plasmodium falciparum malaria, the efficacy testing of asexual blood-stage vaccine candidates in Aotus nancymaae represents a tool to select between different formulations before conducting expensive human clinical trials. CpG oligonucleotides (ODN) specifically promote the production of pro-inflammatory and Th1-type cytokines and they enhance the immunogenicity of co-administered antigens. Toll like receptor 9 (TLR-9) binds directly and sequence-specifically to single-stranded un-methylated CpG-DNA mediating the biological effects of CpG ODN. We cloned and functionally characterised the TLR-9 cDNA of A. nancymaae. The cDNA encompassed 3,099 bp predicted to code for 1,032 amino acid residues. Results of homology searches to human TLR-9 suggested that the receptor is 93 and 94% identical at the nucleotide and amino acid sequence levels, respectively. Stimulation of splenocytes of A. nancymaae with CpG ODN resulted in proliferative responses in all animals analysed. FACS analysis of cultures incubated with CpG ODN 2006 indicated that the B cell marker CD20 was up-regulated consistent with B cell activation. The high level of sequence conservation of Aona-TLR-9 reinforces the suitability of A. nancymaae as animal model for malaria subunit vaccine development.

Amino Acid Sequence↗

PubMed2001

Pathogenesis of RSV lower respiratory tract infection: implications for vaccine development.

Respiratory syncytial virus (RSV) infection is the most prevalent cause of severe respiratory disease in infants. It also causes considerable morbidity in older children and adults with underlying risk factors. RSV vaccine development has been complicated by the need to administer the vaccine at a very young age and by enhanced disease observed after vaccination with formalin inactivated RSV. For infants live attenuated vaccines, which may not be expected to predispose for vaccine induced enhanced pathology, hold the greatest promise. However, the balance between attenuation and immunogenicity appears to be delicate. For older risk groups, results with subunit vaccines are most promising.

Antibodies, Viral↗

PubMed2003

A joint clinical research center in Thailand: role in HIV vaccine development.

In 1992 the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, collaborated with the Phramongkutklao Army Medical Center to set up the Joint Clinical Research Center (JCRC). The purpose of the Center is to conduct clinical research in support of HIV vaccine development and testing. To date, eight HIV vaccine-related research protocols have been conducted at the JCRC, involving 1,668 volunteers. The JCRC has been, and continues to be, a key site for the transfer of clinical trial expertise to new sites at universities, government clinics and hospitals in Thailand and other countries. Overall rates of follow-up have been excellent, while protocol violations and data clarification errors have been minimal.

AIDS Vaccines↗

PubMed2003

Molecular host-pathogen interaction in brucellosis: current understanding and future approaches to vaccine development for mice and humans.

Brucellosis caused by Brucella spp. is a major zoonotic disease. Control of brucellosis in agricultural animals is a prerequisite for the prevention of this disease in human beings. Recently, Brucella melitensis was declared by the Centers for Disease Control and Prevention to be one of three major bioterrorist agents due to the expense required for the treatment of human brucellosis patients. Also, the economic agricultural loss due to bovine brucellosis emphasizes the financial impact of brucellosis in society. Thus, vaccination might efficiently solve this disease. Currently, B. abortus RB51 and B. melitensis REV.1 are used to immunize cattle and to immunize goats and sheep, respectively, in many countries. However, these genetically undefined strains still induce abortion and persistent infection, raising questions of safety and efficiency. In fact, the REV.1 vaccine is quite virulent and apparently unstable, creating the need for improved vaccines for B. melitensis. In addition, Brucella spp. may or may not provide cross-protection against infection by heterologous Brucella species, hampering the acceleration of vaccine development. This review provides our current understanding of Brucella pathogenesis and host immunity for the development of genetically defined efficient vaccine strains. Additionally, conditions required for an effective Brucella vaccine strain as well as the future research direction needed to investigate Brucella pathogenesis and host immunity are postulated.

Animals↗

PubMedDate not supplied

Human immunodeficiency virus vaccine development in developing countries: are efficacy trials feasible?

The implementation of human immunodeficiency virus (HIV) vaccine efficacy trials in developing countries represents an unprecedented series of challenges for the medical and scientific communities, health authorities, policy makers, and the populations of diverse countries. Such trials require great attention, dedication, and information at the earliest possible time from many groups in these communities, as well as the clear and full collaboration of all the national and international institutions and agencies involved. This article discusses suggestions and makes recommendations regarding multiple hurdles to trial implementation, including access to appropriate populations, incidence and natural history of HRV type 1 (HIV-1) infection, definition of efficacy endpoints, and logistical, ethical, regulatory, political, and media issues. The conduct of phase I and II trials in developing countries will be a critical step for appropriate vaccine selection and in helping to identify the country- and community-specific issues and the needs for further implementation. Some countries have already established their own national HIV vaccine development plans. Additional operational and action plans with special emphasis on efficacy trial implementation would be strongly recommended after country-specific preparedness workshops and constitution of national or regional task forces.

AIDS Vaccines↗

PubMed1999

Immunoglobulin-binding proteins in ticks: new target for vaccine development against a blood-feeding parasite.

Humans have a long history of trying to control ticks. At first, attempts focused on modifying the habitat, whereas later efforts relied heavily on the use of chemicals. Current research is directed at finding a vaccine against ticks. A strategy of targeting 'concealed antigens' succeeded with the first commercialised vaccine against the cattle tick Boophilus microplus. However, vaccine development against other tick species appears unsatisfactory to date. Vaccination depends on a specific antibody-mediated immunoreaction that damages the parasite. Immunoglobulin molecules of vertebrate hosts can pass through gut barriers into the haemolymph of ectoparasites while retaining antibody activity. Research on the ixodid tick Rhipicephalus appendiculatus revealed that host immunoglobulin-G in the parasite was excreted via salivation, during feeding. Immunoglobulin-binding proteins in tick haemolymph and salivary glands are thought to be responsible for such excretion. The discovery of an immunoglobulin excretion system in ticks indicates that they have a highly developed mechanism to protect themselves from their host's antibody attack. Such a mechanism questions whether immunization strategies will be effective against ticks, unless they circumvent or disable the ticks' immunoglobulin excretion system.

Amino Acid Sequence↗

PubMed1996

Genetic manipulation of Vibrio cholerae for vaccine development: construction of live attenuated El Tor candidate vaccine strains.

The recent spread of El Tor cholera to America augments the need for an effective, safe and economical vaccine. In the present paper we describe the construction of live attenuated V. Cholerae strains by specifically deleting the genes encoding cholera toxin and other putative toxins from the bacterial chromosome. To maximize the likelihood of exposing protective antigens relevant to currently circulating vibrios we selected for genetic manipulation recent epidemic V. cholerae isolates from Peru. The mutant strains did not produce cholera toxin in vitro and in vivo. Deletion of the virulence cassette was accompanied by marked attenuation in the infant mouse cholera model. A selected El Tor Ogawa candidate vaccine strain was refractory to acquisition of foreign genes by conjugation with toxigenic vibrios.

Animals↗

PubMed2004

Application of biotechnological tools for coccidia vaccine development.

Coccidiosis is a ubiquitous intestinal protozoan infection of poultry seriously impairing the growth and feed utilization of infected animals. Conventional disease control strategies have relied on prophylactic medication. Due to the continual emergence of drug resistant parasites in the field and increasing incidence of broiler condemnations due to coccidia, novel approaches are urgently needed to reduce economic losses. Understanding the basic biology of host-parasite interactions and protective intestinal immune mechanisms, as well as characterization of host and parasite genes and proteins involved in eliciting protective host responses are crucial for the development of new control strategy. This review will highlight recent developments in coccidiosis research with special emphasis on the utilization of cutting edge techniques in molecular/cell biology, immunology, and functional genomics in coccidia vaccine development. The information will enhance our understanding of host-parasite biology, mucosal immunology, and host and parasite genomics in the development of a practical and effective control strategy against Eimeria and design of nutritional interventions to maximize growth under the stress caused by vaccination or infection. Furthermore, successful identification of quantitative economic traits associated with disease resistance to coccidiosis will provide poultry breeders with a novel selection strategy for development of genetically stable, coccidiosis-resistant chickens, thereby increasing the production efficiency.

Animals↗

PubMed1994

[Helicobacter pylori and molecular biology--virulence, diagnosis and vaccine development].

The discovery of H. pylori as the etiologic agent of chronic antral type B gastritis and the finding that H.pylori is involved in the pathogenesis of gastroduodenal ulcer disease and gastric carcinoma have triggered intensive research about this organism. After overcoming considerable initial difficulties, researchers succeeded in adapting the instruments of molecular biology to the study of this highly fastidious organism. This has led to a rapid increase of knowledge concerning the basis of H.pylori virulence (as well as that of the related animal pathogens H. mustelae and H. felis) and to the development of molecular methods for the purposes of diagnosis and epidemiological research. The latest application of molecular biology in this area is the use of recombinant proteins for the development of an H.pylori vaccine. This review gives an overview of this rapidly developing field.

Bacterial Vaccines↗

PubMed2003

Rational peptide-based tumour vaccine development and T cell monitoring.

Antigen-specific vaccination is a promising emerging treatment option for cancer patients. Results from early clinical vaccination trials with tumour peptides in patients with metastatic disease have shown tumour regressions in few patients usually with limited disease. Current clinical studies focus on the development of more potent vaccination strategies and on the vaccination of patients with occult or small volume metastatic disease. The novel generation of sensitive T-cell assays allowing direct quantitation and characterisation of specific T cells provide an essential tool for further systematic clinical development of vaccine protocols. There is accumulating evidence from clinical cancer vaccination trials of a relation between the induction of specific T cells and clinical efficacy.

Adjuvants, Immunologic↗

PubMed2006

Optimization of the delivery of heterologous proteins by the Salmonella enterica serovar Typhimurium type III secretion system for vaccine development.

Type III protein secretion systems, which are organelles with the capacity to deliver bacterial proteins into host cells, have been adapted to deliver heterologous antigens for vaccine development. A limitation of these antigen delivery systems is that some proteins are not amenable to secretion through this pathway. We show here that proteins from the simian and human immunodeficiency viruses that are not permissive for secretion through a Salmonella enterica serovar Typhimurium type III secretion system can be modified to travel this secretion pathway by introduction of discrete mutations. Proteins optimized for secretion were presented more efficiently via the major histocompatibility complex class I pathway and were able to induce a better immune response.

AIDS Vaccines↗

PubMed2000

Engrafting costimulator molecules onto tumor cell surfaces with chelator lipids: a potentially convenient approach in cancer vaccine development.

The genetic modification of cells to develop cell-based vaccines and to modulate immune responses in vivo can be risky and inconvenient to perform in clinical situations. A novel chelator lipid, nitrilotriacetic acid di-tetradecylamine (NTA-DTDA) that, via the NTA group has high affinity for 6His peptide, was used to directly anchor recombinant forms of T cell costimulatory molecules containing a C-terminal 6-His sequence onto tumor cell surfaces. Initial experiments using murine P815 tumor cells established the optimum conditions for incorporating NTA-DTDA onto the membranes of cells. P815 cells with incorporated NTA-DTDAbound hexahistidine-(6His)-tagged forms of the extracellular domains of murine B7.1 and CD40 (B7.1-6H and CD40-6H) at very high levels (fluorescence 200-300-fold above background), and both proteins could be anchored onto the cells simultaneously. Significant loss of the anchored or "engrafted" protein occurred through membrane internalization following culture of the cells under physiological conditions, but P815 cells with engrafted B7.1-6H and/or CD40-6H stimulated the proliferation of allogenic and syngeneic splenic T cells in vitro, and generated cytotoxic T cells when used as vaccines in syngeneic animals. Furthermore, the immunization of syngeneic mice with P815 cells engrafted with B7.1-6H or with B7. 1-6H and CD40-6H induced protection against challenge with the native P815 tumor. The results indicate that the use of chelator lipids like NTD-DTDA to engraft costimulatory and/or other molecules onto cell membranes could provide a convenient alternative to transfection in the development of cell-based vaccines and for modulation of immune function.

Amines↗

PubMed2005

SARS vaccine development.

Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines.

Epitopes↗

PubMed1988

Plasmodium vivax malaria: parasite biology defines potential targets for vaccine development.

Although progress in the development of an antimalarial vaccine has been mostly obtained through the study of P. falciparum, significant advances have recently been made in the study of P. vivax, the other major human malarial parasite. Antigens which have been shown to be important in P. falciparum have been characterized and in some cases cloned in P. vivax. Other studies have examined some of the more specific biological characteristics of P. vivax. Among these are studies on components present in caveolae--vesicle complexes of the infected erythrocyte, on the occurrence of delayed hepatic development leading to relapse, or on the Duffy erythrocyte antigen as a key receptor for parasite invasion. Although progress has been made in the short-term in vitro maintenance of P. vivax, the inability to maintain the parasite in continuous culture led to the investigation of wild parasite populations in patients; occurrence of extensive antigenic and karyotype polymorphism was detected in this way, as was a double-blocking and enhancing activity of human antibodies on parasite development in the vector. The association of monoclonal antibodies with DNA recombinant technology allowed the characterization of a number of P. vivax antigens to be made. Among these, an antigen shared between sexual and asexual stages was shown to constitute a target for transmission-blocking immunity. The cloning of an antigen involved in transmission-blocking immunity, along with that of the surface antigen of the sporozoite (CSP) and of a major surface antigen of the invasive merozoite (PV200) constitutes a significant step towards the development of a multivalent recombinant vaccine against P. vivax.

Animals↗