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 1,045 records · Page 58Linked to original sources
PubMed1997

United States vaccine research: a delicate fabric of public and private collaboration. National Vaccine Advisory Committee.

In the last 20 years, two thirds of all new vaccines provided worldwide have been produced by a US network of independent industrial, governmental, and academic partners engaged in vaccine research and development. Vaccines are complex products and the science of vaccinology is difficult. To achieve the full promise of modern science and technology to prevent and treat disease by immunization, the delicate fabric of America's cooperative and collaborative vaccine research relationships must be sustained and strengthened. The major partners are the federal government; four large companies--two US-headquartered (Wyeth-Lederle Biologics and Vaccines and Merck & Co), two foreign firms (SmithKline Beecham and Pasteur Mérieux Connaught); and academia. Of the $1.4 billion that fund US vaccine research and development annually, 46% comes from vaccine sales, 36% from taxpayers, and 18% from risk capital. Vaccine innovation could be strengthened by improved public and policy maker understanding of the vaccine development network; declarations of partnership; interactive dialog with federal advisory bodies; public forums for government and industry to listen to patients, providers and researchers; sabbatical assignments between partners; mechanisms to share industries' market research with public immunization programs; continued active industry participation in the Advisory committee on Immunization Practices and the National Vaccine Advisory committee; increased collaboration between industry and the National Institutes of Health for clinical research; harmonization of the Advisory Committee on Immunization Practices vaccine recommendations and the Food and Drug Administration package inserts; and public policies to foster the partnership's collaboration and robustness. The optimal size and configuration of the US vaccine enterprise should be debated only in the context of a full understanding of how the current system works and its record of effectiveness. These National Vaccine Advisory Committee recommendations are directed at developing public policies to foster and sustain vaccine innovation and ensure the timely introduction and supply of new vaccines needed by this nation and the world.

Cooperative Behavior↗
PubMed2005

Progress and controversies in developing cancer vaccines.

Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2) and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

Editorial↗
PubMed2003

Problems and solutions to the development of vaccines in the elderly.

Scientists involved in vaccine research and development face the challenge of protecting the ever-increasing elderly population from a broad spectrum of infectious diseases. The optimal vaccine-induced immune response to confer protection is undefined for many pathogens, and the field of vaccine research is undergoing a gradual shift from the original focus on humoral immunity to a focus that incorporates cellular and innate immune components. The age-related changes in various aspects of immune function, including an increase in a population of T cells that shows signs of replicative senescence, underscore the need to enhance research aimed at designing vaccines to meet the unique requirements of the elderly population.

Aged↗
PubMed1991

Molecular parasitology: progress towards the development of vaccines for malaria, filariasis, and schistosomiasis.

Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages of Plasmodium and Schistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed.

Amino Acid Sequence↗
PubMed2005

Risks and benefits of immunizing pregnant women: the risk of doing nothing.

The medical, social and legal risks of immunizing pregnant women are obstacles preventing the initiation of programs to immunize women for their protection and for their infant's protection. Recent projects devoted to vaccine development have focused on protecting newborns and infants. But there are many other reasons for developing or utilizing vaccines before or during pregnancy, beyond the protection of the newborn. Besides the usual reasons for utilizing immunizations to protect the mother and the neonate, the threat of bio-terrorism adds a new dimension to the necessity for addressing this issue. The potential advantages for thinking about vaccinating pregnant women include an array of possible programs associated with risks and benefits. The immunization of pregnant women or women of reproductive age has multiple purposes: to protect the mother, to protect the newborn and infant and to prevent diseases and complications of pregnancy. (1) Preparation of vaccines against infectious agents that are known to result in reproductive pathology and congenital malformation if the infection of the mother occurs during pregnancy. (2) To utilize vaccines used routinely to protect the non-pregnant population, for administration during pregnancy, i.e., influenza, tetanus and other vaccines. Should these vaccines and other routinely used vaccines for children and non-pregnant adults be administered to women during pregnancy if they are medically indicated? (3) Utilization of vaccines to protect women from diseases to which they are susceptible because of pregnancy (poliomyelitis, hepatitis). (4) Utilization of vaccines for use before or during pregnancy, primarily to protect the newborn and infant via maternal transplacental antibodies, i.e., GBD (group B streptococcus). (5) The prevention of intrauterine infection that has been alleged to initiate premature labor. (6) The preparation of a vaccine for use before or during pregnancy to protect both the mother and the neonate, i.e., botulism toxin vaccine. The regulatory agencies and the vaccine producers will need a great deal of objective scientific advice and support and it is the scientific community's responsibility to provide that support. If the scientific and medical community ignores the opportunity to develop vaccines that could reduce the occurrence of reproductive and developmental problems, then we can be accused of acquiescing to the "risk of doing nothing."

Adult↗
PubMed2000

Malaria vaccines.

Although the possibility of a live attenuated malaria vaccine has been considered, current malaria vaccine development activities are dominated by attempts to develop a subunit vaccine. Hence, it is entirely appropriate that a session of the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, was devoted to vaccine development. The oral presentations in this session and the relevant poster presentations are outlined here by Robin Anders and Allan Saul.

Animals↗
PubMed2004

Policy analysis: an essential research tool for the introduction of vaccines in developing countries.

To address the unacceptable levels of disease in developing countries and the lack of vaccines to address infectious diseases, the public sector has been expanding its funding for, and involvement in, vaccine research and development. The public sector is becoming a full participant in the spectrum of translational research taking candidates from the laboratory to use in national immunization programmes. As these programmes and the continuing work of the private sector achieve success, an extensive analysis of policy will be needed to support the introduction of vaccines. Based on the early experience with the introduction of hepatitis B vaccine in several developing countries, there is a defined framework for the introduction of vaccines. This framework lays out five essential overlapping and complementary elements of introduction of vaccines in developing countries. Each element requires a clear understanding of policy-related issues. There is a pressing need to include and expand policy analysis on a wide range of topics to ensure that the poor in developing countries can have access to the fruits of modern biotechnology.

Developing Countries↗
PubMed1999

Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism.

Herein, we review the epitope approach to vaccine development, and discuss how knowledge of HLA supertypes might be used as a tool in the development of such vaccines. After reviewing the main structural features of the A2-, A3-, B7-, and B44- supertype alleles, and biological data demonstrating their immunological relevance, we analyze the frequency at which these supertype alleles are expressed in various ethnicities and discuss the relevance of those observations to vaccine development. Next, the existence of five new supertypes (A1, A24, B27, B58, and B62) is reported. As a result, it is possible to account for the predominance of all known HLA class I with only nine main functional binding specificities. The practical implications of this finding, as well as its relevance to understanding the functional implication of MHC polymorphism in humans, are discussed.

Alleles↗
PubMed2002

[Antitumor vaccines: conception, development and evaluation in humans].

Our strategy is to develop multivalent recombinant vaccines capable of eliciting broad immune responses in patients with malignant melanoma or colorectal cancer. Our current focus is on the induction of tumor-specific T cell responses using a prime-boost immunization schedule with a unique vector system derived from the canarypox virus called ALVAC, in which we incorporate genes encoding Tumor Associated Antigens (TAAs). A series of phase I/II clinical studies evaluating ALVAC recombinants carrying either the CEA, p53, MAGE1 or MAGE3 genes, administered through the subcutaneous, intradermal or intravenous routes, has shown that this approach is safe and can induce tumor-specific antibody or T cell responses in at least some of the patients. Based on these encouraging results, future candidate vaccines will likely target multiple tumor-associated antigens, using several antigen presentation platforms associated in prime-boost immunization regimens.

Animals↗
PubMed2006

Chapter 26: Innovative financing mechanisms to accelerate the introduction of HPV vaccines in developing countries.

The costs of developing and producing new-generation vaccines have increased compared to many of the older, "traditional" vaccines because of new technologies and regulatory requirements. While the public sector often supports basic research costs, private manufacturers are usually responsible for the investments in product development and production scale-up. When considering investments, firms evaluate the probability of a market. Unfortunately, the developing country vaccine market is small (in revenue terms) and often unpredictable, particularly given inaccurate forecasting in the past. Low-income developing countries expect low prices. Demand (actual decisions to pay for and introduce the vaccine) is almost always lower than need (estimates of requirements to achieve optimal public health outcomes), a distinction that may be even more significant for HPV vaccines given the number of new vaccines against priority diseases that will become available over the coming 5 years. One new mechanism under consideration to address some of these challenges is Advanced Market Commitments (AMCs). By providing an assured price subsidy for developing country purchase of a future vaccine meeting predefined standards, an AMC would provide industry with greater assurances of earning a reasonable return on their investment to serve the poorest developing countries. The AMC mechanism could provide critical motivation for increased industry (private) investment that would otherwise not occur. HPV vaccines are one of six vaccines being considered for a possible AMC pilot.

Developing Countries↗
PubMed2000

Biologic approaches to the prevention of sexual transmission of human immunodeficiency virus.

HIV prevention science has made progress, especially in Thailand and some sub-Saharan African countries. New cases of HIV in the United States, however, have not diminished and explosive epidemics in India and the People's Republic of China seem inevitable. Therefore, HIV prevention activities must move forward in parallel. Funding for biologic and behavioral research efforts must be balanced. Behavioral research must inform biologic strategies. In addition, HIV prevention efforts have been distorted by forces that require further consideration. First, the stigmatization associated with a diagnosis of HIV infection led to prevention efforts that virtually ignore the index case. Focusing entirely on the susceptible population puts intense and unrealistic pressure on behavior change and vaccine development. Although development of an HIV vaccine is desirable, there is no evidence that this goal can be achieved in the near future. Blind faith in vaccine technology detracts from pursuit of alternative aspects of prevention science. Vaccine development is but one of several key components to a broad-based prevention strategy. The history of control of infectious diseases has shown the need for targeting index cases. This certainly will prove important in HIV over the next few years. In developed countries, antiretroviral therapy for established HIV infection has become the standard of care. Increased knowledge of the biology of transmission of HIV suggests use of ART to prevent transmission. Such intervention must be accompanied by safer sex behavior in the index cases, and ultimately could lead to some form of monitoring and directly observed therapy. At this time, the latter approach seems unrealistic in developing countries, where the expense of drugs renders them unavailable. But there is every reason to believe that cheaper, more appropriate drugs will be developed before an effective vaccine. Furthermore, targeted use of ART might have disproportionate benefits in some countries. Women are the fastest growing HIV risk group. Several issues, both biologic and social, make this trend a concern. Increases in the number of HIV-infected women will lead to greater vertical transmission. Women possibly have different risk factors for acquisition and transmission than men. Information about the effects of vaginal ecology, specifically, the role of bacterial vaginosis, in the acquisition of HIV is essential because bacterial vaginosis can be reversed, at least transiently. To allow women to take an active role in HIV prevention methods, development of a topical microbicide is vital and may prove easier than a vaccine. Finally, HIV prevention efforts require knowledgeable, central leadership. All prevention efforts should be developed and implemented in parallel, to gain a synergistic result. Few vaccine experts are enthusiastic about microbicides, and HIV caregivers only rarely focus on the public health considerations of their patients. Stopping the spread of HIV requires a coordinated, concerted efforts using "all the tools in the toolbox."

AIDS Vaccines↗
PubMed2005

Anthrax vaccines: a development update.

The current human anthrax vaccines licensed in the US and UK consist of aluminum hydroxide-adsorbed or alum-precipitated culture supernatant material from fermentor cultures of toxigenic noncapsulated strains of Bacillus anthracis. The threat of B. anthracis being used as a biowarfare agent has led to a wider usage of these vaccines, which has heightened concerns regarding the need for frequent boosters and the occasional local reactogenicity associated with vaccination. These concerns have provided the impetus for the development of better characterized vaccines. This review summarizes the work of numerous laboratories in the search for alternative vaccines against anthrax that are well tolerated, provide long-lasting immunity, and are efficacious.

Animals↗
PubMed2003

Two years into reverse vaccinology.

During the last century, several approaches have been used for the development of vaccines, going from the immunization with live-attenuated bacteria up to the formulation of the safer subunit vaccines. This conventional approach to vaccine development requires cultivation of the pathogen and its dissection using biochemical, immunological and microbiological methods. Although successful in several cases, this method is time-consuming and failed to provide a solution for many human pathogens. Now genomic approaches allow for the design of vaccines starting from the prediction of all antigens in silico, independently of their abundance and without the need to grow the microorganism in vitro. A new strategy, termed "Reverse Vaccinology", which has been successfully applied in the last few years, has revolutionized the approach to vaccine research. The Neisseria meningitidis serogroup B project, the first example of Reverse Vaccinology, as well as the application of this strategy to develop novel vaccines against other human pathogens are discussed.

Bacterial Vaccines↗
PubMedDate not supplied

Development of vaccines against malaria.

Substantial progress towards development of a vaccine against Plasmodium falciparum malaria has been accomplished. A number of vaccine candidate antigens have been identified and in some of these antigens immunodominant B-cell and T-cell epitopes have been defined. New adjuvants and delivery systems suitable for human vaccines are available. The selection of suitable epitopes and their assembly in multi-antigenic constructs are research tasks for the future.

Amino Acid Sequence↗
PubMed1995

Immunization of dairy cows with an Escherichia coli J5 lipopolysaccharide vaccine.

Development of a lipopolysaccharide-protein conjugate vaccine and the immunological response to the vaccine were investigated. Lipopolysaccharide derived from Escherichia coli J5 was detoxified by mild alkaline hydrolysis. Detoxification reduced endotoxin activity 2500-fold compared with that of native J5 lipopolysaccharide. The conjugate vaccine was synthesized by covalently coupling detoxified lipopolysaccharide to chicken serum albumin by reductive amination. Dairy cows were immunized with 8.35 mg of conjugate (n = 3) or 5 x 10(9) heat-killed J5 bacterin (n = 5) at 215 DIM and received a secondary immunization 14 d later. Control cows were not immunized. Immunization enhanced serum antibody titer to J5 lipopolysaccharide antigens. Whey IgG and IgM titers to J5 lipopolysaccharide were not different among treatment groups. Serum and whey IgG titers to J5 whole-cell antigens were elevated in immunized cows within treatment groups. Immunization did not enhance whey IgM to J5 whole-cell antigens. Conjugate immunization elicited an immune response comparable with or greater than that of immunized cows with J5 bacterin.

Animals↗
PubMed1996

Immunogenicity of zona pellucida vaccines.

Development of zona pellucida (ZP) based contraceptive vaccines raises a number of complications that challenge current immunological capabilities. Our research examines two aspects of these immunological problems. First, recent studies demonstrate that one bacterially expressed rabbit ZP recombinant vaccine (rec55) induces autoantibodies in primates that prevent sperm-ZP binding and induction of the acrosome reaction in the homologous ZP in vitro. Immunization with rec55 does not induce ovarian pathology, and the duration of antibody titres indicates that this vaccine would have reversible effects on fertility. However, the immunogenicity of the rec55 protein produced in the pEX bacterial expression vector is low. We have therefore expressed the cDNA encoding rec55 using the pGEX vector for the following reasons: (i) the pGEX expressed recombinant proteins are soluble in aqueous solution; (ii) affinity purification of recombinant proteins on glutathione Sepharose columns is more effective for obtaining larger quantities of purified protein; and (iii) the availability of protease cleavage sites between the ZP and glutathione S transferase fusion proteins should eliminate the possibility of carrier-mediated suppression of immune responses. These improvements in protein production and purification yield immunogen which is more malleable to immunological studies. Second, while it is clear that ZP recombinant vaccines can eliminate the problem of ovarian pathology, it is important to understand how such pathology results from immunization with native ZP proteins and certain recombinant ZP proteins. To this end, we have initiated immunization studies in baboons comparing rabbit ZP and pig ZP immunogens in Titremax adjuvant. Unilateral ovariectomies at different time points after immunization (1.5, 2, 4 and 6 months) will allow studies on the time course of pathology within the ovary. Comparison of these results with ongoing rabbit ZP immunizations will help elucidate the differences in immunogenicity of ZP proteins isolated from the two species.

Animals↗
PubMed1992

Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine.

Plasmid pTETnir15, which directs the expression of the non-toxic immunogenic fragment C of tetanus toxin from the anaerobically inducible nirB promoter, was introduced into the Salmonella typhimurium aroA aroD live oral vaccine strain BRD509. The resulting strain, designated BRD847, was used to vaccinate orally BALB/c mice and was tested for plasmid stability and its ability to protect against a lethal tetanus toxin challenge. pTETnir15 was stably inherited by bacteria growing or persisting in the tissues of immunized mice whereas another BRD509 derivative, designated BRD753, harboring plasmid pTET85 which directs fragment C expression from the tac promoter, was highly unstable. Mice immunized with a single oral dose of BRD847 developed high levels of circulating anti-fragment C antibodies and were solidly protected against tetanus toxin challenge. Mice immunized with a single oral dose of BRD753 developed no detectable anti-fragment C antibodies. After boosting, antibodies were detected, but the mice were only partially protected against tetanus toxin challenge. Thus the use of an in vivo inducible promoter such as nirB may be a generally applicable approach to obtaining the stable in vivo expression of heterologous antigens in Salmonella vaccine strains.

Anaerobiosis↗