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PubMedDate not supplied

A scientific overview of the development of AIDS vaccines.

This article explores the development of AIDS vaccines. It briefly describes the differences between cellular and humoral immune systems and their role in HIV disease. It also considers the use of animal models in vaccine research to simulate human immune system responses to HIV. In addition, various vaccine strategies are explained. These strategies include live attenuated vaccines, subunit vaccines, live vector-based vaccines, DNA vaccines, pseudovirions, whole inactivated virus, and combination products. Advantages and disadvantages for each strategy will be described as well as the current state of progress in vaccine development. The purpose of this article is to educate nurses and other health care providers about the recent developments in vaccine technology as well as to encourage all health care providers to advocate for increased research and development of HIV-1 vaccines.

AIDS Vaccines↗

PubMed2001

Induction of T lymphocyte responses to dengue virus by a candidate tetravalent live attenuated dengue virus vaccine.

Development of a safe and immunogenic tetravalent dengue virus (DV) vaccine has been designated as a priority by the World Health Organization. We characterized the T cell response to DV induced by a candidate live attenuated tetravalent DV vaccine as part of a phase I study. Proliferation and cytotoxic T lymphocyte (CTL) responses to multiple DV serotypes were detected in six of six and four of four subjects studied, respectively. Proliferation responses were higher to DV serotypes 1 and 3 than to serotypes 2 and 4. CTL responses were higher to DV serotypes 2 and 3 than to serotype 1, and included serotype cross-reactive responses. Production of interferon-gamma, but not IL-4, was observed in response to DV stimulation. This candidate vaccine is immunogenic for both CD4+ and CD8+ T lymphocytes. However, T cell responses to the four DV serotypes were not equivalent, suggesting that the vaccine could be further optimized.

Antibodies, Viral↗

PubMed1999

The introduction of new vaccines into developing countries.

The development and introduction of new vaccines is a costly and time consuming process. Unfortunately, those most in need--individuals in developing countries--are the last to receive these powerful disease preventing products. From the time a vaccine is first licensed in a developed country to the time most of the poor in developing countries have access to the vaccine can be 20-30 years. This delay is unacceptable. There is a great need to reduce this time span. This paper examines five ways of reducing the time span. Each of the five is essential and achieving success on all five will require a heightened level of international effort and coordination.

Developing Countries↗

PubMed1994

Enhancement of EIAV replication and disease by immunization with a baculovirus-expressed recombinant envelope surface glycoprotein.

The potential for antibody-dependent enhancement of replication of macrophage/monocyte tropic viruses has posed a significant problem in the development of vaccines for several animal and human viruses and has raised significant concern in the design of potential AIDS vaccines. Using the previously described equine infectious anemia virus/Shetland pony system as a model for HIV-1 vaccine development, we have evaluated the efficacy of a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein (gp90) of EIAV. The results of these trials demonstrate not only that the recombinant vaccine failed to protect against infection by standard homologous and heterologous EIAV challenge strains, but that it resulted in a marked enhancement of virus replication and exacerbation of disease in immunized ponies exposed to the heterologous virus strain. Thus, the recombinant EIAV gp90 vaccine provides a novel in vivo model for examining in detail the mechanisms of immune enhancement of a lentivirus infection and for evaluating strategies to avoid the production of deleterious immune responses in AIDS vaccine design.

AIDS Vaccines↗

PubMed1996

Evaluating new vaccines for developing countries. Efficacy or effectiveness?

Despite the profusion of promising new vaccines against illnesses prevalent in developing countries, uncertainties about the balance between costs and benefits of new vaccines have retarded their use in public health practice. Conventional prelicensure trials of vaccine protection exacerbate these uncertainties by focusing on measurement of vaccine efficacy--the performance of a vaccine under idealized conditions. Vaccine effectiveness trials provide a more pragmatic perspective by addressing the performance of a vaccine under the ordinary conditions of a public health program, by capturing direct as well as indirect effects of vaccination, and by comprehensively addressing outcomes of public health concern. The use of effectiveness trials should enable more rational triaging of new vaccines for developing countries and may accelerate the introduction of new vaccines into public health practice by resolving speculative debates about practical costs and benefits.

Case-Control Studies↗

PubMed1993

Experiences with a vaccine being developed for the control of swine dysentery.

A prototype vaccine that is being developed for the control of swine dysentery (SD) was tested in two groups of experimental pigs. Vaccination induced high circulating antibody titres against the aetiological agent, Serpulina (Treponema) hyodysenteriae. Pigs in the first trial were vaccinated twice before being challenged orally with the bacteria. Five of 6 unvaccinated animals developed dysentery within a fortnight of challenge, but only 1 of 6 vaccinated pigs showed signs of disease at this time. Unexpectedly, 1 mo after challenge, the surviving unvaccinated pig and 2 remaining healthy vaccinated animals succumbed to the disease. The reason for the development of this late-onset form of dysentery was not clear. In the second trial, 8 pigs were vaccinated 3 times. Only 2 of these animals (25%) developed severe dysentery after being mixed with infected pigs, whereas 7 of 8 (88%) unvaccinated control pigs in the same pen became diseased. The late-onset form of dysentery was not observed. The prototype vaccine for SD provided a useful level of protection, and could be used in programs to control the disease in Australia.

Animals↗

PubMed2001

History of vaccines and positioning of current trends.

The history of vaccine development spans a relatively short period of time in comparison to the history of human civilization. However, monumental advances in the field of vaccines have been made in effort to combat infectious disease. These advances have led to a reduction, and in one case the complete eradication, of the burden of some infectious diseases of the world. Throughout the history of vaccine development, milestone discoveries can be identified that have shaped the field of vaccine development, as we know it. These milestones include the first official use of a vaccine by Edward Jenner, the attenuation principals observed by Pasteur, the development of cell culture for the propagation of viruses, and the production of first recombinant protein based vaccine for hepatitis B. As vaccine development progresses into the 21st century, it will be important to build on the experience and knowledge generated in the past, in an effort to surpass the limitations that currently hamper the development of new and more effective vaccine technologies. Presented here is an overview on the history of vaccine development and its influence on the positioning of current trends and future considerations.

Adjuvants, Immunologic↗

PubMed2005

Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines.

A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine development is standardization of reagents and assays for evaluation of immune responses elicited by candidate vaccines. To provide a panel of viral reagents from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded in peripheral blood mononuclear cells and characterized both genetically and biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each from CRF01_AE and CRF02_AG were prepared from individuals whose HIV-1 infection was evaluated by complete genome sequencing. The main criterion for selection was that the candidate isolate was pure clade or pure circulating recombinant. After expansion in culture, the complete envelope (gp160) of each isolate was verified by sequencing. The 50% tissue culture infectious dose and p24 antigen concentration for each viral stock were determined; no correlation between these two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates. Isolates were also screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies, and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium-inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest that the panel contains both neutralization-sensitive and -resistant isolates. This collection of HIV-1 isolates represents the six major globally prevalent strains, is exceptionally large and well characterized, and provides an important resource for standardization of immunogenicity assessment in HIV-1 vaccine trials.

AIDS Vaccines↗

PubMed2000

Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice.

The continual threat posed by newly emerging influenza virus strains is demonstrated by the recent outbreak of H5N1 influenza virus in Hong Kong. Currently, immunization against influenza virus infection is fairly adequate, but it is imperative that improved vaccines are developed that can protect against a variety of strains and be generated rapidly. Since humoral immunity is ineffective against serologically distinct viruses, one strategy would be to develop vaccines that emphasize cellular immunity. Here we report the successful protection of C57BL/6 mice from a lethal A/HK/156/97 (HK156) infection by immunizing first with an H9N2 isolate, A/Quail/HK/G1/97 (QHKG1), that harbours internal genes 98% homologous to HK156. This strategy also protected mice that are deficient in antibody production, indicating that the immunity is T-cell-mediated. In the course of these studies, we generated a highly pathogenic H5N1 reassortant which implicated NP and PB2 as having an important contribution to pathogenesis when present with a highly cleavable H5. These results provide the first demonstration that protective cell-mediated immunity can be established against the highly virulent HK156 virus and have important implications for the development of novel strategies for the prevention and treatment of HK156 infection and the design of future influenza vaccines.

Animals↗

PubMed2005

The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice.

We have investigated to develop novel vaccines against SARS CoV using cDNA constructs encoding the structural antigen; spike protein (S), membrane protein (M), envelope protein (E), or nucleocapsid (N) protein, derived from SARS CoV. Mice vaccinated with SARS-N or -M DNA using pcDNA 3.1(+) plasmid vector showed T cell immune responses (CTL induction and proliferation) against N or M protein, respectively. CTL responses were also detected to SARS DNA-transfected type II alveolar epithelial cells (T7 cell clone), which are thought to be initial target cells for SARS virus infection in human. To determine whether these DNA vaccines could induce T cell immune responses in humans as well as in mice, SCID-PBL/hu mice was immunized with these DNA vaccines. As expected, virus-specific CTL responses and T cell proliferation were induced from human T cells. SARS-N and SARS-M DNA vaccines and SCID-PBL/hu mouse model will be important in the development of protective vaccines.

Animals↗

PubMed2006

Vaccines under development: group B streptococcus, herpes-zoster, HIV, malaria and dengue.

OBJECTIVES: To review the current state of development of streptococcus B, herpes-zoster, HIV, malaria and dengue vaccines. These vaccines were selected both because of imminent commercial release and because of specific problems with their development. SOURCES OF DATA: A review of the literature was performed by means of a MEDLINE search, on the period 1996 to 2006, for the epidemiology and immunology of these diseases, analyzing both the greatest obstacles to creating a vaccine and the current state of research, with emphasis on studies in the most advanced stages. SUMMARY OF THE FINDINGS: Each of the five diseases chosen presents specific problems for vaccine development. Nevertheless, in the majority of cases these have been or are in sight of being resolved, allowing for the prediction that a safe and effective vaccine - or vaccines - will be available in the near future. CONCLUSIONS: Despite the problems faced in developing these vaccines, advances in molecular biology and immunology have made it possible to overcome most obstacles, opening up the prospects for new vaccines.

AIDS Vaccines↗

PubMed2006

[Diarrhea and vaccines: current developments].

Diarrhoea is a main concern for travellers, populations of developing countries and children. Causative pathogens are numerous. An efficient vaccine against cholera is available, also offering a 50% cross-protection against E. Coli enterotoxin (ETEC), however its efficacy is only 23% against all-causes traveller's diarrhoea. Rotavirus can be responsible for severe diarrhoea in infants but rarely causes traveller's diarrhoea. Two new vaccines being under development appear effective and well-tolerated but too expensive for developing countries which most need them. To date, the live oral Ty21a vaccine remains frequently prescribed in Switzerland, with limited indications and suboptimal efficacy. A new oral vaccine is under development.

Bacterial Vaccines↗

PubMed2005

Introducing new vaccines into developing countries: obstacles, opportunities and complexities.

Infectious diseases are thought to account for nearly 25% of all deaths worldwide, and extract a disproportionate toll in developing countries. Moreover, infectious diseases are now appreciated to be major causes of the poverty and economic underdevelopment that characterize the world's poorest countries. Development and deployment of new vaccines to prevent infectious diseases in developing countries have therefore become high priorities in the global health agenda.

Developing Countries↗

PubMed1984

Hepatitis B vaccine in developing countries: problems and prospects.

Hepatitis B vaccines are highly immunogenic. To determine the efficacy of low doses and of the intradermal route of vaccination, 197 Nigerian children were given 3 monthly doses of Hevac B. Of these, 96 had 2 micrograms subcutaneously and 101 had 2 micrograms intradermally. One month after completing the schedule, 82.3% and 74.3% of the respective groups had become anti-HBs positive without adverse side-effects. In the second part of the study, 50 chronic HBsAg carriers were vaccinated. Compared to placebo-treated carriers, no effect was demonstrated with regard to HBsAg clearance or anti-HBs production. Immune complexes were not attributable to Hevac B. No untoward effects were noted. Booster vaccination of 50 initial non-responders resulted in the development of significant levels of anti-HBs in 20 (40%) of the recipients. None of the 'non-responders' developed clinical or virological evidence of HBV infection. It is concluded that low-dose vaccination is effective and that the intradermal route may be useful in developing countries.

Adolescent↗

PubMed1987

Development of vaccines against shigellosis: memorandum from a WHO meeting.

Endemic shigellosis is a worldwide problem, with a high morbidity rate in most developing countries; substantial mortality may also occur, especially with disease caused by Shigella dysenteriae serotype 1. The limited efficacy of current measures to control this infection makes the development of vaccines for the prevention of shigellosis particularly important. This Memorandum describes the clinical features of and immunity to shigellosis, summarizes the present status of efforts to develop suitable vaccines, and lists the topics that should be given priority in research.

Bacterial Vaccines↗

PubMed1998

Staphylococcus aureus: a well-armed pathogen.

Staphylococcus aureus is a virulent pathogen that is currently the most common cause of infections in hospitalized patients. S. aureus infection can involve any organ system. The success of S. aureus as a pathogen and its ability to cause such a wide range of infections are the result of its extensive virulence factors. The increase in the resistance of this virulent pathogen to antibacterial agents, coupled with its increasing prevalence as a nosocomial pathogen, is of major concern. The core resistance phenotype that seems to be most associated with the persistence of S. aureus in the hospital is methicillin resistance. Methicillin resistance in nosocomial S. aureus isolates has been increasing dramatically in United States hospitals and is also associated with resistance to other useful antistaphylococcal compounds. Possible ways to decrease the incidence of nosocomial S. aureus infections include instituting more effective infection control, decreasing nasal colonization, developing vaccines, and developing new or improved antimicrobials.

Cross Infection↗

PubMed2001

Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines.

Tumors expressing a high level of certain types of tumor-associated carbohydrate antigens (TACAs) exhibit greater metastasis and progression than those expressing low level of TACAs, as reflected in decreased patient survival rate. Well-documented examples of such TACAs are: (i) H/Le(y)/Le(a) in primary non-small cell lung carcinoma; (ii) sialyl-Le(x) (SLe(x)) and sialyl-Le(a) (SLe(a)) in various types of cancer; (iii) Tn and sialyl-Tn in colorectal, lung, breast, and many other cancers; (iv) GM2, GD2, and GD3 gangliosides in neuroectodermal tumors (melanoma and neuroblastoma); (v) globo-H in breast, ovarian, and prostate cancer; (vi) disialylgalactosylgloboside in renal cell carcinoma. Some glycosylations and TACAs suppress invasiveness and metastatic potential. Well-documented examples are: (i) blood group A antigen in primary lung carcinoma; (ii) bisecting beta1 --> 4GlcNAc of N-linked structure in melanoma and other cancers; (iii) galactosylgloboside (GalGb4) in seminoma. The biochemical mechanisms by which the above glycosylation changes promote or suppress tumor metastasis and invasion are mostly unknown. A few exceptional cases in which we have some knowledge are: (i) SLe(x) and SLe(a) function as E-selectin epitopes promoting tumor cell interaction with endothelial cells; (ii) some tumor cells interact through binding of TACA to specific proteins other than selectin, or to specific carbohydrate expressed on endothelial cells or other target cells (carbohydrate-carbohydrate interaction); (iii) functional modification of adhesive receptor (integrin, cadherin, CD44) by glycosylation. So far, a few successful cases of anti-cancer vaccine in clinical trials have been reported, employing TACAs whose expression enhances malignancy. Examples are STn for suppression of breast cancer, GM2 and GD3 for melanoma, and globo-H for prostate cancer. Vaccine development canbe extended using other TACAs, with the following criteria for success: (i) the antigen is expressed highly on tumor cells; (ii) high antibody production depending on two factors: (a) clustering of antigen used in vaccine; (b) choice of appropriate carrier protein or lipid; (iii) high T cell response depending on choice of appropriate carrier protein or lipid; (iv) expression of the same antigen in normal epithelial tissues (e.g., renal, intestinal, colorectal) may not pose a major obstacle, i.e., these tissues are not damaged during immune response. Idiotypic anti-carbohydrate antibodies that mimic the surface profile of carbohydrate antigens, when administered to patients, elicit anti-carbohydrate antibody response, thus providing an effect similar to that of TACAs for suppression of tumor progression. An extension of this idea is the use of peptide mimetics of TACAs, based on phage display random peptide library. Although examples are so far highly limited, use of such "mimotopes" as immunogens may overcome the weak immunogenicity of TACAs in general.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed2003

[SARS, possible zoonosis in the area of conflict of pathogenic coronaviruses of animals].

Severe acute respiratory syndrome (SARS) is an emerging disease, which was first recognized in Guangdong Province, China, in November 2002. In the meantime, SARS has been recognized in patients on all five continents. A novel coronavirus, which is not related to the hitherto known coronaviruses, has been proven to be associated with the disease. Our genomic analyses strongly suggest that the new SARS-coronavirus did not emerge through mutation or recombination and that it has probably been transmitted from a so far not identified animal species to humans. Therefore, it is most likely that SARS virus is a zoonotic agent. A broad body of knowledge originating from research in veterinary medicine indicates that development of vaccines against the SARS-coronavirus may be problematic. The potential danger of such vaccines should not be neglected during the process of vaccine development.

Animals↗