PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Vaccine Development”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

Chlamydia trachomatis infection: incidence, health costs and prospects for vaccine development.

Chlamydia trachomatis infection is now the most common sexually transmitted disease worldwide. World Health Organisation figures estimated that 89 million new cases of genital Chlamydia infections occurred in 1995, highlighting the worldwide prevalence of infections and the economic burden on healthcare delivery. A number of methods have been developed for detection of chlamydial infection, which vary in sensitivity and specificity. No single method has yet gained general acceptance and in many countries Chlamydia infections are not reported, suggesting that the above figures may be an underestimate of the problem. As yet there is no consensus as to what constitutes a protective immune response against genital Chlamydia infection. Studies in animal models have shown that cell-mediated immunity, both Th1-driven macrophage activation and cytotoxic T cell responses, as well as antibody can mediate protection at different stages of the chlamydial life cycle. A successful vaccine would probably need to elicit both a systemic cell-mediated immune response to limit/resolve established infections and a mucosal IgA response to reduce bacterial shedding and the resulting spread of infection to partners of infected individuals. The immune response to Chlamydia, either through natural infection or following immunisation, also has the potential to enhance inflammation and to act as a driving force for constant mutation in the variable regions of the major outer membrane protein. As a result a constant prevalence of infection is maintained even in an immune population through the emergence of new allelic variants. Immune responses against antigens such as the 60 kDa heat shock protein can exacerbate inflammation through molecular mimicry and must not be elicited as a result of vaccination. Thus there are many challenges for the development of a successful vaccine which must elicit immunity against multiple serovars while at the same time minimising damaging pro-inflammatory immune responses.

Animals↗

Genetic rearrangements leading to disruption of heterologous gene expression in mycobacteria: an observation with Escherichia coli beta-galactosidase in Mycobacterium smegmatis and its implication in vaccine development.

Different mycobacteria carrying cloned genes for heterologous protective antigens have been proposed as vaccine vehicles. In this study, the stability of the expression of beta-galactosidase was studied in Mycobacterium smegmatis using integrative (pMV361::lacZ) and replicative (pMV261::lacZ) vectors. Recombinant M. smegmatis forms blue colonies on X-gal plates. Occasional white mutants encountered while plating on X-gal plates were genetically analysed. The loss of lacZ phenotype was due to insertion of an IS element in lacZ gene of integrative vector whereas in case of replicative vectors, loss of lacZ phenotype was due to deletions of different sizes in the lacZ gene and the Phsp60 promoter region. The frequency of such events was rare, 1.7 x 10(-5) in integrative vector and 2 x 10(-3) in the case of replicative vector. The integrative vector seemed more stable in terms of expression of foreign genes in mycobacteria. Hence, the rearrangements reported in the present study warrant serious consideration before implementing mycobacteria as recombinant vaccines.

Bacterial Vaccines↗

Optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development.

Enterovirus 71 (EV71) is an enterovirus that could lead to severe neurological disorders and fatalities. The inactivated vaccine is an appropriate EV71 vaccine format for meeting current needs. Large-scale preparation of the inactivated EV71vaccine depends on a scalable cell culture system for industrial mass production. In this paper, Vero cells were found to produce higher titers of EV71 than did MRC-5 and WI-38 cells. High-density microcarrier Vero cell cultures were established using 5g/L Cytodex 1 microcarriers and found to promote the release of EV71s from infected Vero cells. For the large-scale production of the inactivated vaccine antigen, the extracellular virus titers produced in the 2L bioreactor were found to be 10 times lower than the spinner flask culture but improved by 30-folds using glucose/glutamine feedings during infection. A serum-free Vero cell microcarrier culture was also established in the bioreactor, yielding a high-titer of 5.8 x 10(7) TCID50/mL for EV71 production. The immunogenicity of the inactivated virions produced in serum-free culture elicited a slightly higher level of neutralizing antibody response in immunized mice. These results constitute valuable information on the development of a large-scale microcarrier cell culture process for producing inactivated EV71 vaccine.

Animals↗

Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain.

In order to evaluate the immunogenicity and protective efficacy of anthrax vaccine candidates a suitable small animal model is required. The inbred A/J strain of mouse has been selected as a potential model, and its immune response to immunisation with recombinant protective antigen (rPA) vaccine characterised, by assessment of rPA specific antibody production, and protection against injected challenge, with the unencapsulated STI strain of Bacillus anthracis. Studies were conducted to determine the time required post immunisation to develop a protective immune response, to define the minimum protective dose of vaccine required and to assess the long-term immune response to immunisation. From the results of these studies it was possible to establish that the A/J mouse is a consistent and robust small animal model for rPA vaccine testing. A comparison of the immune response to rPA vaccine immunisation in the Turner Outbred (TO) mouse strain was also conducted. Both inbred and outbred mouse strains displayed a predominantly Th2 biased immune response and showed a comparable antibody response to rPA immunisation. An assessment of protection in the TO mouse against aerosol challenge with the fully virulent strain of B. anthracis, Ames, was also made.

Animals↗