Overview of vaccines and vaccination

Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the kind of the immune responses generated by those vaccines, which are so effective. To date, all licensed vaccines generate especially specific antibodies, which attach to the infectious agent and therefore can very largely prevent infection. These vaccines have been so effective in developed countries in preventing mortality after a subsequent infection that attempts are being made to develop vaccines against many of the remaining infectious agents. Many of the latter are difficult to manipulate; they can cause persisting infections or show great antigenic variation. A range of new approaches to improve selected immune responses, such as immunization with DNA or chimeric live vectors, viral or bacterial, are under intense scrutiny, as well as genomic analysis of the agent.     

Vaccines against protozoal diseases of veterinary importance

Abstract Protozoan parasites are important animal and human pathogens. At present, most of these infections are controlled by chemotherapy. In addition, vaccines are available for some of these diseases. There is, however, still an urgent need for the development of vaccines against protozoal diseases, since the current array of available vaccines is very limited. This review describes the different approaches that have been taken to develop such vaccines and discusses the difficulties that hampered vaccine development. Many of the problems are related to the complex life cycle of these parasites and the virtual lack of mass in vitro culture systems. We also give an overview of the commercial and non-commercial vaccines that do exist at present. Finally, we describe the future directions of this interesting field. New techniques and strategies include parasite cultivation methods and recombinant-DNA techniques, such as vector vaccines and DNA-vaccines. Moreover, these approaches are complemented by the development of sophisticated adjuvants; the coupling of immunoprotective molecules to entities with adjuvant activity or the use of cytokines, e.g. IL-12. Through these innovations new vaccines against protozoal diseases will become available in the near future.     

Transgenic plants for the production of veterinary vaccines

The expression of antigens in transgenic plants has been increasingly used in the development of experimental vaccines, particularly oriented to the development of edible vaccines. Hence, this technology becomes highly suitable to express immunogenic proteins from pathogens. Foot and mouth disease virus, bovine rotavirus and bovine viral diarrhoea virus are considered to be the most important causative agents of economic loss of cattle production in Argentina, and they are thus optimal candidates for alternative means of immunization. Here, we present a review of our results corresponding to the expression of immunogenic proteins from these three viruses in alfalfa transgenic plants, and we discuss the possibility of using them for the development of plant-based vaccines.     

Conquering sexually transmitted diseases

Sexually transmitted diseases (STDs) are a major public-health problem and also a significant financial burden on the economy. Past and ongoing attempts to create vaccines against sexually transmitted pathogens have met with varying success. This article highlights some of the public-health and social problems that are associated with STDs and the technical and ethical challenges in treating them, and raises several questions that need to be addressed if STDs are to be conquered.     

Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines

We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against intravenous challenge by the cloned homologous virus E11S but that this protection was only partially effective against the uncloned virus, SIVmne. In the present study, we examine the protective efficacy of this immunization regimen against infection by a mucosal route. We found that the same gp160-based vaccines were highly effective against intrarectal infection not only with the E11S clone but also with the uncloned SIVmne. Protection against mucosal infection is therefore achievable by parenteral immunization with recombinant envelope vaccines. Protection appears to correlate with high levels of SIV-specific antibodies and, in animals protected against the uncloned virus, the presence of serum-neutralizing activities. To understand the basis for the differential efficacies against the uncloned virus by the intravenous versus the intrarectal routes, we examined viral sequences recovered from the peripheral blood mononuclear cells of animals early after infection by both routes. We previously showed that the majority (85%) of the uncloned SIVmne challenge stock contained V1 sequences homologous to the molecular clone from which the vaccines were made (E11S type), with the remainder (15%) containing multiple conserved changes (the variant types). In contrast to intravenously infected animals, from which either E11S-type or the variant type V1 sequences could be recovered in significant proportions, animals infected intrarectally had predominantly E11S-type sequences. Preferential transmission or amplification of the E11S-type viruses may therefore account in part for the enhanced efficacy of the recombinant gp160 vaccines against the uncloned virus challenge by the intrarectal route compared with the intravenous route.     

Respiratory Viruses—Current Status and Future Prospects

The application of tissue culture technology has revealed several new groups of viruses, comprising scores of different serotypes, as important causes of upper and lower respiratory tract disease in man. Other agents as yet unrecognized undoubtedly exist.Present epidemiologic data, although still incomplete, point up the unique importance of certain of these viruses in respiratory diseases.The particular type and severity of respiratory syndrome produced by a virus is determined by the immune status of the host, by the presence of complicating disease and by characteristics intrinsic in the infecting agent itself.Respiratory virus control might be particularly beneficial in certain groups, particularly persons with allergic sensitivity and chronic pulmonary disease.For control of viral respiratory disease, active immunization would provide significant protection but highly polyvalent vaccines might be necessary. Adjuvants could be helpful in this regard.Certain vaccines formerly in use were produced from strains of viruses which have recently been shown to be oncogenic in animals. In addition, hybridization of viruses can occur, resulting in the incorporation of the oncogenic potential of one agent into the genetic constitution of another. The significance of these biologic phenomena to vaccination programs has yet to be defined.Passive immunization would provide short-lived protection and would find application only in uniquely susceptible populations or at times of augmented risk. Active immunization of pregnant women, however, could provide increased breadth and duration to the transplacental passive immunity in the newborn.Interferon-inducing agents could potentially provide broad spectrum antiviral protection, but the extent and duration of their effectiveness are unknowns.Certain chemical agents have been shown to have prophylactic and therapeutic effects against a limited number of clinically severe viral diseases. Finally, limited data suggest that climatic control in places of public gathering might be worth evaluating as a means of controlling the spread of viral respiratory infections.     

Vaccine-induced immunopathology during bovine respiratory syncytial virus infection: exploring the parameters of pathogenesis

The bovine and human respiratory syncytial viruses cause severe lower respiratory tract infections. Effective vaccines against the respiratory syncytial viruses have been lacking since vaccine failures in the 1960s and 1970s. In this report, we describe a bovine respiratory syncytial virus (bRSV) challenge model in which both classical bRSV respiratory infection and vaccine-enhanced immune pathology were reproduced. The classical, formalin-inactivated (FI) bRSV vaccine that has been associated with vaccine failure was efficient in inducing high antibody titers and reducing viral loads but also primed calves for a far more serious enhanced respiratory disease after a bRSV challenge, thereby mimicking the enhanced clinical situation in FI human RSV (hRSV)-immunized and hRSV-infected infants in the 1960s. We show that immunization with FI-bRSV mainly primes a Th2-like inflammatory response that is characterized by a significant eosinophilic influx in the bronchial alveolar lung fluid and lung tissues and high levels of immunoglobulin E serum antibodies. The current model may be useful in the evaluation of new bRSV candidate vaccines for potency and safety.     

Extended immunization intervals enhance the immunogenicity and protective efficacy of plasmid DNA vaccines

Effective vaccines against infectious diseases and biological warfare agents remain an urgent public health priority. Studies have characterized the differentiation of effector and memory T cells and identified a subset of T cells capable of conferring enhanced protective immunity against pathogen challenge. We hypothesized that the kinetics of T cell differentiation influences the immunogenicity and protective efficacy of plasmid DNA vaccines, and tested this hypothesis in the Plasmodium yoelii murine model of malaria. We found that increasing the interval between immunizations significantly enhanced the frequency and magnitude of CD8+ and CD4+ T cell responses as well as protective immunity against sporozoite challenge. Moreover, the interval between immunizations was more important than the total number of immunizations. Immunization interval had a significantly greater impact on T cell responses and protective immunity than on antibody responses. With prolonged immunization intervals, T cell responses induced by homologous DNA only regimens achieved levels similar to those induced by heterologous DNA prime/ virus boost immunization at standard intervals. Our studies establish that the dosing interval significantly impacts the immunogenicity and protective efficacy of plasmid DNA vaccines.     

Perspectives of development of immunoprophylaxis in Russia

Analytic materials on prevention of controlled infections in Russia and perspectives for extension of immunoprophylaxis field are presented. It was determined that immunization against pertussis should be expanded. Necessity to include vaccines against hepatitis A, Hib, pneumococcal infection, varicella as well as rotavirus and human papillomavirus infection in National immunization schedule is substantiated. It was noted that introduction of new vaccines will require both increase of funding for immunization and switch on use of combination vaccines containing 4 - 6 components.     

Protective effect of antiganglioside antibodies against experimental Trypanosoma brucei infection in mice

Liposome-associated ganglioside antigens (ganglioside GM1 or bovine brain gangliosides) were prepared to facilitate the potential protective efficacy for Trypanosoma brucei. Mice were immunized with liposome-associated ganglioside GM1 or bovine brain gangliosides intraperitoneally (i.p.). After immunization, significantly higher antigen-specific IgG and IgM antibodies were detected in sera than in the nonimmunized control group. When sera from immunized mice were analyzed for isotype distribution, antigen-specific IgG1, IgG2a, and IgG3 antibody responses were also noted. After immunization, mice were challenged i.p. with 1 x 10(2) cells of T. brucei. Sixty percentage of liposome-associated ganglioside GM1-immunized mice survived the infection, and all the mice immunized with bovine brain gangliosides-containing liposomes survived. However, all control mice died within 7 days after infection. These data demonstrate that liposomes containing ganglioside antigens have the potential usefulness for the induction of a protective immune response against T. brucei infection and suggest the possibility of developing vaccines that may ultimately be used for the prevention of trypanosomiasis.     

Approaches To New Vaccines

ABSTRACT:?

The explosive technological advances in the fields of immunology and molecular biology in the last 5 years had an enormous impact on the identification of candidate vaccines against diseases, which until a few years ago seemed uncontrollable. Increased knowledge of the immune system has helped to define the mechanisms that underlie successful immunization and is now being exploited to develop improved versions of existing vaccines and new vaccines against emerging pathogens, tumors, or autoimmune diseases. An understanding of the mechanisms of action of novel adjuvants and the development of new vector and delivery systems will have a major impact on vaccine strategies. The use of DNA encoding antigens from pathogenic viruses, bacteria, and parasites as vaccines is a new approach that is receiving considerable attention. This and other innovative approaches, including vaccine production in plants, are appraised in this review. The successful eradication of smallpox and the imminent eradication of poliomyelitis by worldwide immunization campaigns provide positive examples of how the vaccine-mediated approach can lead to disease elimination; with the advent of new vaccines and improved delivery systems, there is no scientific reason why these successes cannot be repeated.     

联合疫苗应用现状及评价*

联合疫苗含有两种或多种免疫原（活的、灭活的病原体或者提纯的抗原）,用于预防多种疾病或由同一病原体的不同亚型或血清型引起的疾病,可以避免常规免疫多次注射的问题。然而和单价疫苗相比,联合疫苗研发的复杂性大大增加,将多种免疫原混合到一起进行免疫时不同免疫原间可能因为物理、化学和免疫学机制而干扰其他免疫原的免疫反应,此外佐剂和防腐剂等非活性成分也可能对联合后的活性成分产生影响,这就对联合疫苗的评价提出了特别的要求。本文对联合疫苗的研究应用现状、临床评价和发展前景等方面做一综述。     

Mucosal immunization with live recombinant bovine respiratory syncytial virus (BRSV) and recombinant BRSV lacking the envelope glycoprotein G protects against challenge with wild-type BRSV

Recombinant bovine respiratory syncytial virus (rBRSV) and an rBRSV deletion mutant lacking the G gene (rBRSVDeltaG) were characterized in calves with respect to replication competence, attenuation, and protective efficacy as live-attenuated BRSV vaccines. Both recombinant viruses were safe and induced protection against a BRSV challenge infection. rBRSV replicated efficiently in the upper respiratory tract. Intranasal immunization with rBRSVDeltaG led to infection but not to mucosal virus replication. Neutralizing antibodies were induced by rBRSV and rBRSVDeltaG. Thus, the BRSV attachment glycoprotein G seems to be dispensable in vaccinating calves against BRSV.     

Oral vaccines: new needs, new possibilities

Vaccination is an important tool for handling healthcare programs both in developed and developing countries. The current global scenario calls for a more-efficacious, acceptable, cost-effective and reliable method of immunization for many fatal diseases. It is hoped that the adoption of oral vaccines will help to provide an effective vaccination strategy, especially in developing countries. Mucosal immunity generated by oral vaccines can serve as a strong first line of defense against most of the pathogens infecting through the mucosal lining. Advances in elucidating the mechanism of action of oral vaccines will facilitate the design of more effective, new generation vaccines. There are promising developments in the use of different agents to effectively deliver the vaccine candidate. It is hoped that ongoing research may be able to set another cardinal point, after polio vaccine, in eradicating infectious diseases.     

Development of vaccines to control bovine tuberculosis in cattle and relationship to vaccine development for other intracellular pathogens

Vaccination of cattle against bovine tuberculosis could be an important strategy for the control of disease either where there is a wildlife reservoir of Mycobacterium bovis infection or in developing countries where it is not economically feasible to implement a 'test and slaughter' control program. Advances in the understanding of protective immune responses to M. bovis infection in cattle and the advent of new molecular biological techniques, coupled with the sequencing of the M. bovis genome have provided opportunities for the rational development of improved tuberculosis vaccines. A number of new tuberculosis vaccines including attenuated M. bovis strains, killed mycobacteria, protein and DNA vaccines are under development and many are being assessed in cattle. Recent results have revealed several promising vaccine candidates and vaccination strategies. Ways of distinguishing between vaccinated and infected cattle are becoming available and the possibility of new approaches to the eradication of tuberculosis from domestic livestock is discussed. Similarities between the mechanisms of protective immunity against M. bovis and against other intracellular parasites continue to be found and discoveries from vaccine studies on bovine tuberculosis may provide helpful insights into requirements for vaccines against other intracellular pathogens.     

Serotype-independent protection against pneumococcal infections elicited by intranasal immunization with ethanol-killed pneumococcal strain,SPY1

The 23-valent polysaccharide vaccine and the 7-valent pneumococcal conjugate vaccine are licensed vaccines that protect against pneumococcal infections worldwide. However, the incidence of pneumococcal diseases remains high in low-income countries. Whole-cell vaccines with high safety and strong immunogenicity may be a favorable choice. We previously obtained a capsule-deficient Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an attenuated live pneumococcal vaccine, intranasal immunization with SPY1 elicits broad serotype-independent protection against pneumococcal infection. In this study, for safety consideration, we inactivated SPY1 with 70% ethanol and intranasally immunized BALB/c mice with killed SPY1 plus cholera toxin adjuvant for four times. Results showed that intranasal immunization with inactivated SPY1 induced strong humoral and cellular immune responses. Intranasal immunization with inactivated SPY1 plus cholera toxin adjuvant elicited effective serotype-independent protection against the colonization of pneumococcal strains 19F and 4 as well as lethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 against lethal pneumococcal infection were comparable to those of currently used polysaccharide vaccines. In addition, vaccine-specific B-cell and T-cell immune responses mediated the protection elicited by SPY1. In conclusion, the 70% ethanol-inactivated pneumococcal whole-cell vaccine SPY1 is a potentially safe and less complex vaccine strategy that offers broad protection against S. pneumoniae.     

Vaccination against the major infectious diseases

The reputation of vaccination rests on a 200-year-old history of success against major infectious diseases. That success has led to the doctrine of 'for each disease, a vaccine'. Although some diseases have proved frustrating, this doctrine carries considerable truth. However, when one reviews the vaccines now available it is apparent that most successes have been obtained when the microbe has a bacteremic or viremic phase during which it is susceptible to the action of neutralizing antibodies, and before replication in the particular organ to which it is tropic. Poliomyelitis and infections by capsulated bacteria are examples where vaccination has worked efficiently. However, some success has also been achieved against agents replicating on respiratory or gastrointestinal mucosae. Influenza, pertussis and rotavirus vaccines are examples of such agents, against which it has been possible to induce immune responses acting locally as well as systemically. In addition, when bacteria produce disease through exotoxins, purification and chemical or genetic inactivation of those toxins has yielded highly efficacious vaccines. Control of intracellular pathogens has not been achieved, except partly with the BCG vaccine against tuberculosis, and modern efforts are directed towards pathogens against which cellular immune responses are critical. In general, two achievements have been crucial to the success of vaccines: the induction of long-lasting immunological memory in individuals and the stimulation of a herd immunity that enhances control of infectious diseases in populations.     

Leptospirosis vaccines

Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.     

Serologic surveillance for selected viral agents in captive and free-ranging populations of Arabian oryx (Oryx leucoryx) from Saudi Arabia and the United Arab Emirates

A total of 294 sera collected between 1999 and 2001 from eight captive and one free-ranging herds of Arabian oryx (Oryx leucoryx) distributed in Saudi Arabia (SA) and the United Arab Emirates (UAE) were assayed for antibodies against 13 selected viral agents. Arabian oryx have been exposed to bluetongue virus (BTV), epizootic hemorrhagic disease virus (EHDV), rinderpest virus (RPV), bovine respiratory syncytial virus (BRSV), bovine adenovirus 3 (BAV-3), cervid herpesvirus-1, foot-and-mouth disease virus, equine herpesvirus 9, and bovine viral diarrhea virus. The high seroprevalence to BTV and EHDV in the UAE and SA indicates that Arabian oryx are likely to be susceptible to infection by these viruses and therefore could act as a source of virus to vectors during the infective stage of infection. Moreover, antibodies were detected against RPV and BRSV in sera from SA and against BAV-3 in sera from the UAE. No antibodies were found against bovine herpesvirus-1, caprine herpesvirus-1, enzootic bovine leucosis virus, and peste des petits ruminants virus. On the basis of these results, caution should be applied when considering translocation of Arabian oryx, and only those proven to be free of infectious agents that might present a risk to other species should be moved.