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At least 343 records · Page 19Linked to original sources
PubMed2005

Application of the polyvalent approach to HIV-1 vaccine development.

One major obstacle to the design of a global HIV-1 vaccine is viral diversity. Presently, data suggest that a single antigen will not suffice to generate broadly reactive neutralizing antibodies to protect all individuals against all subtypes of HIV-1 infection. While some of the neutralizing epitopes are identified in the constant regions of the HIV-1 envelope (Env) glycoprotein, many are localized to variable regions and differ conformationally from one virus to the next. The successes of polyvalent vaccine approaches against other antigenically variable pathogens encourage adoption of the same approach for HIV-1 vaccine design. The critical question is which envelope antigens should be combined in a vaccine cocktail to provide maximum protection against HIV-1. A review of the existing human vaccines based on the polyvalent principle is included here to provide a historical perspective for the current effort of developing a polyvalent HIV-1 vaccine. Data generated from several groups actively working on candidate polyvalent HIV-1 vaccines are summarized. Information presented in this review highlights the potential and importance of the polyvalent vaccine approach for the future development of an effective HIV-1 vaccine.

AIDS Vaccines↗
PubMed1999

Immunity and vaccine development in the bovine theilerioses.

There are three economically important bovine Theileria species: Theileria annulata, which causes tropical theileriosis and occurs across north Africa and most of central Asia; Theileria parva, which causes East Coast fever and is found in East and Central Africa; and Theileria sergenti, which is predominantly a problem in Japan and Korea. Theileria annulata preferentially infects macrophages in vivo. It is controlled largely by means of live, attenuated vaccines, which are produced by prolonged tissue culture of the schizont-infected cells. The immunity induced in animals, which have either recovered from an infection or have been vaccinated (with an attenuated vaccine), is broad, solid and cell mediated. It is considered that the main effector cells are cytostatic macrophages that produce nitric oxide. Subsidiary roles for bovine leucocyte antigen (BoLA)-restricted, transiently appearing, cytotoxic T cells, and possibly also natural killer (NK) cells, have been identified. Cytokines such as tumour necrosis factor alpha (TNF-alpha) may have important roles, particularly in the induction of pathology. Matrix metalloproteinases have been implicated in the metastatic behaviour of schizont-infected cells. The nature of the protective schizont target antigens remains unknown. Attempts to develop a subunit vaccine have focused upon a sporozoite antigen (SPAG-1) and a merozoite antigen (Tams1). Both SPAG-1 and Tams1 have given partial protection using different delivery systems and adjuvants, but further vaccine development will probably require identification of a range of other antigens, especially from the schizont stage. Theileria parva has a tropism for T cells. Vaccination is currently by the 'infection and treatment' method, which involves challenging with a controlled dose of sporozoite stabilate and the simultaneous administration of long-acting tetracyclines. The immunity thus induced is mediated by BoLA-restricted cytotoxic T cells, which recognize polymorphic schizont antigens. These antigens have not been characterized at the molecular level. However, the polymorphic nature of the target antigens underlies the fact that the immunity is very strain specific--a situation that distinguishes T. parva from T. annulata. Interestingly, it is not possible to produce an attenuated vaccine to T. parva, as T. parva requires up to two orders of magnitude more schizonts in order to achieve transfer to the new host. A suggested reason for this is that the macrophage targets of T. annulata are phagocytes and thus the schizont has a natural, efficient route of entry whilst the preferred host of T. parva is the non-phagocytic T cell. Analysis of the cytotoxic T-cell response has revealed evidence of BoLA haplotype dominance plus competition between parasite epitopes. Subunit vaccination using a recombinant sporozoite antigen (p67) has proved very promising, with levels of protection of the order of 70% being achieved. A proportion of the protected calves exhibits complete sterile immunity. Interestingly, the basis for this immunity is not clear, since there is no correlation between the titre of antibodies that inhibit sporozoite penetration of lymphocytes and protection. Similarly, there is no significant T-cell response that distinguishes the protected and susceptible animals. These data are very encouraging, but other components, particularly those derived from the schizont, need to be identified and characterized. The mild Theileria species of Japan and Korea (termed T. sergenti in the literature) cause fever and severe chronic anaemia. The schizont stage of the life cycle is very rare and the host cell type is not known. The pathology is associated with chronic piroplasm infection. Immunity can be induced by immunizing with crude piroplasm extracts. Serological analysis of immune sera reveals that the immunodominant antigen is a polypeptide of 30-33 kDa, which corresponds to the protective T. annulata polypeptide Tams1. (ABSTRACT T

Animals↗
PubMed2001

Vaccination with CTL epitopes that escape: an alternative approach to HIV vaccine development?

This article describes a novel approach to HIV vaccine design that is, as yet, unproven and still in preliminary development. In rhesus macaques infected with simian immunodeficiency virus (SIV), we have identified particular cellular immune responses that select for viral variants during primary infection. We speculate that the detection of viral variants with altered amino acids in CTL epitopes implies the successful clearance of cells harboring wild-type virus. Here, we present our rationale suggesting why such potent early CTL responses that exert an antiviral effect may be particularly attractive targets for induction by candidate vaccines. Conventional wisdom suggests that regions of the virus that are structurally and functionally important will generally be well-conserved both among clades and within an infected host. Amino acid replacements within these well-conserved regions should be difficult for the virus to accommodate. Therefore, these regions are traditionally considered ideal targets for vaccine induced immune responses because they are refractory to CTL escape mutations. Many examples of these regions have been identified in both HIV-1 and SIV(mac) (J. Immunol. 162 (1999) 3727; J. Virol. 67 (1993) 438) and have been included in candidate vaccine formulations. Human clinical trials testing these vaccines are currently underway. Our proposed method of vaccination with CTL epitopes that escape explores an alternative hypothesis. Rather than engendering responses to regions of the virus that do not escape, we reason that vaccination needs to accelerate the development of the initial immune responses that effectively select for amino acid variants during acute infection. By examining CTL escape during the acute phase, we will identify CTL responses that the virus cannot tolerate and incorporate these responses into vaccines.

AIDS Vaccines↗
PubMed1994

The promise of asexual malaria vaccine development.

This review presents several reasons to support the belief that an asexual vaccine for human malaria caused by Plasmodium falciparum will be developed. It lists many of the current vaccine candidates that we think are ready for human trials and it summarizes a strategy for the development of an asexual vaccine.

Animals↗
PubMed2003

Live recombinant vectors for AIDS vaccine development.

Live recombinant vectors entered the AIDS vaccine field with the realization that live attenuated HIV vaccines posed too great a safety risk, and that subunit vaccines elicited antibodies which lacked the breadth or potency needed to induce sterilizing immunity. Vectored vaccines provided a means to bring the cellular arm of the immune system into play by mimicking natural viral infection. By delivering antigens within host cells, processing and presentation could occur for induction of cellular immune responses. This recombinant vector approach, either alone or combined with other strategies, has produced impressive results. Recombinants have been generated from DNA and RNA viruses and bacteria. With few exceptions, each vector poses some risk, yet each possesses unique features that make it attractive. In addition to safety, key considerations in vector selection have included previous success as a vaccine against the wild-type agent or other pathogens; ability to induce potent, persistent immune responses; ability to target mucosal inductive sites and antigen presenting cells; lack of integration into the host genome; presence of pre-existing immunity in people; ease of mucosal administration; cloning capacity; ease of engineering and production; and stability of the final product. Here we up-date the status of several live recombinant vectors that have shown good potential in pre-clinical studies. Some have progressed to human clinical trials, and others will shortly. The abundance of vectors, coupled with the complexity arising from use of combination regimens with other vaccine types and heterologous vectors, will necessitate selection of the most promising candidates for large-scale efficacy trials in people. The sooner comparative studies can be designed and implemented in which live recombinant vectors containing the same inserted genes are evaluated head-to-head, the closer we will be to an eventual vaccine.

AIDS Vaccines↗
PubMed1994

Bacteriophages as tools for vaccine development.

The construction of live recombinant bacterial vaccines requires a reasonably sophisticated genetic system for the introduction, stabilization and expression of foreign antigen genes. Bacteriophages offer a rich collection of tools that can be used for vaccine construction, including site-specific integration-proficient vectors, non-antibiotic selectable markers and signals for efficient transcription and translation of foreign genes. We describe the characterization of a temperate phage of the mycobacteria, mycobacteriophage L5, and application of these phage studies for the construction of recombinant BCG vaccines.

BCG Vaccine↗
PubMed2002

Rotavirus vaccines: development, current issues and future prospects.

The potential benefit of safe and effective rotavirus vaccination in reducing morbidity and especially mortality from rotavirus gastroenteritis among children in developing countries has long been recognised. More recently, the focus of attention shifted to developed countries, where cost-effectiveness analyses justified the routine introduction of rotavirus vaccines into childhood immunisation schedules. The recent withdrawal in the U.S.A. of the first licensed rotavirus vaccine (the tetravalent rhesus reassortant rotavirus vaccine), following investigation into reports of intussusception among a number of vaccinees, has directed attention once more towards rotavirus vaccine use in developing countries. However, issues relating to vaccine safety, efficacy, and cost, remain to be overcome before widespread introduction of rotavirus vaccines can be anticipated.

Developing Countries↗
PubMed1996

Selection of rotavirus VP7 gene in the genetic background of simian rotavirus SA11: implications for rotavirus reassortant vaccine development.

We previously reported that the VP7 gene from simian rotavirus SA11 with G-serotype 3(G3-VP7 gene) was preferentially selected in the genetic background of SA11 compared with the G1- or G2-VP7 gene. In the present study, selection of the G4-VP7 gene in competition with G1-, G2- or G3-VP7 gene in the SA11 background was analyzed through mixed infection experiments using SA11 and SA11-human rotavirus single-VP7 gene-substitution reassortants with G-serotypes 1, 2, and 4 (G1-, G2- and G4-reassortant). In virus clones from coinfection of SA11 and G4-reassortant, the frequency of G4 virus decreased to 7% at the 3rd passage and the G4 virus disappeared at the 10th passage, whereas the majority of the clones possessed G3 specificity. However, the predominance of either of the viruses coinfected was not observed in the mixed infection with G4-reassortant and G1- or G2-reassortant. Although growth kinetics of SA11 and G4-reassortant was similar, G4-reassortant showed significantly smaller plaque size than SA11, G1- and G2-reassortant did. These results indicated that the G3-VP7 gene from SA11 might be preferentially selected in the SA11 genetic background compared with the G4-VP7 gene, and suggested that the introduction of a single G4-VP7 gene may affect growth characteristics of recipient virus SA11. These results together with our previous findings suggested the significance of genetic compatibility between recipient viral genes and foreign VP7 gene in the development of multivalent reassortant rotavirus vaccines.

Animals↗
PubMed2005

Genetic diversity of anaplasma species major surface proteins and implications for anaplasmosis serodiagnosis and vaccine development.

The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes several pathogens of veterinary and human medical importance. An understanding of the diversity of Anaplasma major surface proteins (MSPs), including those MSPs that modulate infection, development of persistent infections, and transmission of pathogens by ticks, is derived in part, by characterization and phylogenetic analyses of geographic strains. Information concerning the genetic diversity of Anaplasma spp. MSPs will likely influence the development of serodiagnostic assays and vaccine strategies for the control of anaplasmosis.

Anaplasma marginale↗
PubMed2000

Current tuberculosis vaccine development.

Information derived from the complete genome sequence of Mycobacterium tuberculosis makes it possible to develop a range of new vaccine candidates. Strategies currently under investigation include construction of whole cell live attenuated mycobacterial vaccines, as well as the use of individual antigens delivered by a variety of subunit vaccination procedures. Fundamental questions associated with the rational design, preclinical testing, and future application of new tuberculosis vaccines are reviewed.

Animals↗
PubMed2001

The Jezierski papers: live polio vaccine development in colobus monkey cells but not chimpanzee cells in the Belgian Congo, 1952-1958.

A reading of ten relevant papers by Alexandre Jezierski provides evidence for the only attempt in Central Africa to develop a live oral polio vaccine (OPV) from growing reference wild polio strains to 210 passages in colobus monkey tissue culture, and experimental administration to about 25 humans. Chimpanzees were used as a human model, but their tissues or kidneys were absent from the passage and production line of the proposed vaccine. Thus, the implication published by Hooper that Jezierski had produced a candidate OPV that might have contained chimpanzee viruses, possibly simian immunodeficiency virus cpz or the precursor of human immunodeficiency virus-1 group M, is incorrect.

Animals↗