Development of FIV-specific cytolytic T-lymphocyte responses in cats upon immunisation with FIV vaccines

Vaccine protection has been achieved in cats against experimental infection with feline immunodeficiency virus (FIV). Such protection has been attributed to FIV-specific humoral immunity, as well as cellular immunity of unknown mechanism(s). Since cell-mediated immunity plays a crucial role in the clearance of viral infections, this study evaluated the role of FIV-specific CTL in vaccine prophylaxis. Cats were immunised with inactivated FIV vaccines, reported to have >90% vaccine efficacy. Significant levels of specific CTL activity were detected following the third immunisation. CTL activity persisted for several months and could be enhanced through a booster immunisation. The levels of CTL activity were comparable to those induced by a recombinant canarypoxvirus based FIV vaccine. These results suggest a possible role for CTL-mediated immunity in vaccine protection against FIV infection in cats.     

Evolutionarily conserved T-cell epitopes on FIV for designing an HIV/AIDS vaccine

This review will discuss the current state of the human HIV-1 vaccine trials including the safety consideration of vaccine composition and difficulties in determining and defining protective immunity and epitopes to HIV-1. Vaccines in animal models of lentivirus infection are compared. In particular, the findings from the prototype FIV vaccine and the HIV-1 protein immunizations studies in cats are discussed, as well as the resulting research regarding a potential HIV-1 vaccine design based on evolutionarily conserved T-cell epitopes.     

FIV vaccine development and its importance to veterinary and human medicine: a review FIV vaccine 2002 update and review

Feline immunodeficiency virus (FIV) is a natural infection of domestic cats that results in acquired immunodeficiency syndrome resembling human immunodeficiency virus (HIV) infection in humans. The worldwide prevalence of FIV infection in domestic cats has been reported to range from 1 to 28%. Hence, an effective FIV vaccine will have an important impact on veterinary medicine in addition to being used as a small animal AIDS model for humans. Since the discovery of FIV reported in 1987, FIV vaccine research has pursued both molecular and conventional vaccine approaches toward the development of a commercial product. Published FIV vaccine trial results from 1998 to the present have been compiled to update the veterinary clinical and research communities on the immunologic and experimental efficacy status of these vaccines. A brief report is included on the outcome of the 10 years of collaborative work between industry and academia which led to recent USDA approval of the first animal lentivirus vaccine, the dual-subtype FIV vaccine. The immunogenicity and efficacy of the experimental prototype, dual-subtype FIV vaccine and the efficacy of the currently approved commercial, dual-subtype FIV vaccine (Fel-O-Vax FIV) are discussed. Potential cross-reactivity complications between commercial FIV diagnostic tests, Idexx Snap Combo Test and Western blot assays, and sera from previously vaccinated cats are also discussed. Finally, recommendations are made for unbiased critical testing of new FIV vaccines, the currently USDA approved vaccine, and future vaccines in development.     

Lessons from the cat: development of vaccines against lentiviruses

Feline immunodeficiency virus (FIV) is a natural infection of domestic cats, which produces a disease with many similarities to human immunodeficiency virus (HIV) infection in man. The virus is an important cause of morbidity and mortality in pet cats worldwide. As such an effective vaccine is desirable both for its use in veterinary medicine and also as a model for the development of an HIV vaccine. A large number of candidate vaccines have been tested against feline immunodeficiency virus. These include inactivated virus and infected cell vaccines, DNA and viral vectored vaccines, subunit and peptide vaccines and vaccines using bacterial vectors. Ultimately, the development of inactivated virus and infected cell vaccines led to the release of the first licensed vaccine against FIV, in 2002. This review highlights some of the difficulties associated with the development of lentiviral vaccines and some of the lessons that have been learned in the FIV model that are of particular relevance to the development of HIV vaccines.     

New challenges for the diagnosis of feline immunodeficiency virus infection.

Vaccination of cats against feline immunodeficiency virus (FIV) with a whole-virus vaccine results in rapid and persistent production of antibodies that are indistinguishable from those used for diagnosis of FIV infection. There are no diagnostic tests available for veterinary practitioners at the present time to resolve the diagnostic dilemma posed by use of whole-virus vaccines for protection of cats against FIV. There is a great need for development of commercially available rapid diagnostic tests that conform to differentiation of infected from vaccinated animals standards.     

4种新城疫油苗蛋鸡免疫力对比试验

为了解不同疫苗生产厂家生产的新城疫灭活疫苗的免疫效果,更好地开展新城疫的免疫工作,选用国内4个厂家所生产的新城疫灭活疫苗,免疫商品蛋鸡,依据免疫前后、攻毒后抗体水平变化趋势和攻毒后对鸡群的保护力,评估4种ND油苗的免疫效果。结果表明:3和4号疫苗组死亡保护力均为100%,而且3号和4号疫苗组产生的抗体水平较高、提升时间较早;而1号和2号疫苗组均有死亡,并且抗体水平与3号和4号疫苗组相比较低。由试验可知,不同生产厂家所生产的ND油苗质量参差不齐,免疫效果有较大差异。     

Present and future of veterinary viral vaccinology: a review

This review deals briefly with some key developments in veterinary vaccinology, lists the types of vaccines that are used for vaccinations commonly performed in food animals as well as in companion animals, and indicates that the practising veterinarian can select the best vaccine by comparing the results of efficacy studies. Diva (Differentiating Infected from Vaccinated Animals; also termed marker) vaccines and companion diagnostic tests have been developed that can be used for progammes aimed to control or eradicate virus infections. Vaccine-induced herd immunity, which can be measured relatively easily when diva vaccines are used, is a crucial issue in such programmes. Current vaccine research follows many routes towards novel vaccines, which can be divided into non-replicating ('killed') and replicating ('live') vaccines. Promising trends are the development of DNA vaccination, vector vaccines, and attenuation of DNA and RNA viruses by DNA technology. The lack of (in vitro) correlates of vaccine protection markedly hampers progress in vaccine research. Various characteristics of an 'ideal' vaccine are listed, such as multivalency and the induction of lifelong immunity after one non-invasive administration in animals with maternal immunity. Future research should be aimed at developing vaccines that approach the ideal as closely as possible and which are directed against diseases not yet controlled by vaccination and against newly emerging diseases.     

Evaluation of inactivated vaccine of the variant 2 (IS-1494 /GI-23) genotype of avian infectious bronchitis

The infectious bronchitis virus (IBV) is the cause of avian infectious bronchitis (IB). IB is one of the most highly contagious diseases, which results in many economic losses in the poultry industry worldwide. The nature of this virus is such that it generates new genotypes continuously. Proper vaccination is the most suitable way of combatting IB. One of the novel genotypes of IBV, which has been circulating in the Middle Eastern countries, is the variant 2 (IS-1494/GI-23) genotype. This study aims to design and produce an autogenous variant 2 vaccines. After isolation and characterization of the Iranian variant 2, the inactivated vaccine was formulated according to the OIE guidelines, and its different aspects (Purity, titration, inactivation, immunization) were evaluated. The designed vaccine passed all of OIE quality control standards. In the assessment process, the protection rate in the groups receiving the variant 2 and commercial vaccines was 67 % and 60 %, respectively. Although the differences were not significant, they indicated better protection, and the viral load in the feces and the kidney of the group receiving the variant 2 vaccine was lower than that in the commercial vaccine. It is suggested that the variant2 strain should be added as one of the local strains to the commercial inactivated vaccines in areas affected by this genotype. The use of this vaccine in layer and breeder flocks can help to protect them against variant 2 during the production phase. Also, the transfer of maternal antibodies to offspring can provide strain-specific immunity for one-day-old chickens.     

Vaccination of cats against feline immunodeficiency virus (FIV): a matter of challenge.

So far, most apparently successful immunodeficiency virus vaccines have only been tested against challenge with cell culture-adapted virus. However, even live priming of cats with feline herpesvirus (FHV) vectors expressing the FIV gag and env gene followed by inactivated booster vaccination with fixed FIX infected cell vaccine proved non-protective against infection with a primary FIV isolate. An effective FIV vaccine for field applications therefore is still not underway.     

禽类DNA疫苗研究进展

新型疫苗的研究对于禽类传染病的防制意义重大。传统疫苗是基于抗原刺激机体产生特异性抗体的原理,它们大多数激发机体的体液免疫,很难启动细胞免疫。脱氧核糖核酸(DNA)疫苗作为第3代疫苗,具备传统疫苗和其它基因工程苗不可比拟的优点,能够诱导全方位的免疫反应且使用更安全更方便,DNA疫苗是将外源基因与真核质粒重组后直接导入细胞内,使外源基因在宿主细胞内表达合成保护性抗原蛋白。这是模拟病毒自然感染提呈过程,既能产生细胞免疫,又能产生体液免疫。文章对DNA疫苗在禽类应用的可行性和应用研究新进展作了综述。     

Efficacy and safety of a feline immunodeficiency virus vaccine

Fel-O-Vax FIV is an inactivated virus vaccine designed as an aid in the prevention of infection of cats, 8 weeks or older, by feline immunodeficiency virus (FIV). It contains two genetically distinct FIV strains. The efficacy of this vaccine was demonstrated in a vaccination-challenge study designed to meet various regulatory requirements for registering the vaccine. Eight-week-old kittens were vaccinated with an immunogenicity vaccine which contained minimal release levels of FIV antigens formulated with a proprietary adjuvant system. Twelve months later, all vaccinates and controls were challenged with a heterologous FIV strain. Following the vigorous challenge exposure, cats were monitored for FIV viremia. It was found that 16% of the vaccinated cats developed viremia while 90% of the controls became persistently infected with FIV, which demonstrated that the vaccine was efficacious and the protective immunity lasted for at least 12 months. The safety of the vaccine was demonstrated by a field safety trial in which only 22 mild reactions of short duration were observed following administering 2051 doses of two pre-licensing serials of Fel-O-Vax FIV to cats of various breeds, ages and vaccination histories. Thus, Fel-O-Vax FIV is safe and efficacious for the prevention of FIV infection in cats.     

动物寄生虫口服疫苗研究进展

寄生虫病严重影响全球人类、动物的健康安全，所带来的经济损失巨大。因此，有必要研制针对寄生虫病的疫苗，以阻断寄生虫病在动物与动物、动物与人类之间的传播。寄生虫存在多种免疫逃避机制，已开发的亚单位疫苗、减毒活疫苗、灭活疫苗均未达到理想的预防效果，且商品化疫苗多为针剂疫苗，普通针剂疫苗操作繁琐、运输储藏要求高且易使动物发生应激，直接影响经济成本，因此在实际生产当中需更多操作简单、便于储存、免疫成本更低的新型疫苗，以有效防控寄生虫病。诸多研究表明口服疫苗操作方便，只需通过口服方式投喂且宿主获得的抗体效价水平较高，有望成为预防寄生虫病的有效手段。口服疫苗是一种新型疫苗，依靠宿主的黏膜免疫系统来产生作用，即通过机体黏膜表面接种便可同时诱导机体产生持久的黏膜免疫、体液免疫和细胞免疫，为宿主提供高效的免疫保护。与传统疫苗相比，口服疫苗最显著的优点就是便于接种且应激小，还能形成强大的黏膜免疫屏障。但胃肠道的环境及易形成免疫耐受等因素也为口服疫苗的开发带来很大的挑战。笔者就黏膜免疫系统与口服疫苗作用机理、近几年寄生虫口服疫苗的研究进展及优点与挑战进行综述，以期为寄生虫口服疫苗的开发提供理论依据。     

Difference between influences of homologous and heterologous maternal antibodies on response to serotype-2 and serotype-3 Marek's disease vaccines

Marek's disease (MD) vaccines representing serotypes 2 (SB-1 strain of MD virus) and 3 (FC-126 strain of turkey herpesvirus) were administered to 1-day-old MD-susceptible chicks that either were free of antibodies or carried maternally derived antibodies against SB-1, FC-126, or a serotype-1 MD virus, CU-2 strain. Homologous antibodies delayed the development of vaccine virus viremias and inhibited vaccinal immunity, as judged by protection against challenge with the virulent JM-10 strain of MD virus 7 days postvaccination. Heterologous antibodies had little effect on vaccine responses. Antibodies were shown to interfere with both cell-associated and cell-free vaccine virus.     

Genetic immunisation of cattle against bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8

Bovine herpesvirus 1 (BoHV-1) has frequently been used as a model for testing parameters affecting DNA immunisation in large animals like cattle. However, the selection of target antigens has been poorly studied, and most of the experiments have been conducted in mice. In the present study, we demonstrated in cattle that a DNA vaccine encoding BoHV-1 glycoprotein gD induces higher neutralising antibody titres than vaccines encoding BoHV-1 gC. Additionally, we show that a DNA vaccine encoding a secreted form of gD induces a higher immune response than a vaccine encoding full-length gD. However, the enhanced immunogenicity associated with the secretion of gD could not be extended to the glycoprotein gC. The current study also describes for the first time the development and the evaluation of a DNA vaccine encoding the major tegument protein VP8. This construct, which is the first BoHV-1 plasmid vaccine candidate that is not directed against a surface glycoprotein, induced a high BoHV-1 specific cellular immunity but no humoral immune response. The calves vaccinated with the constructs encoding full-length and truncated gD showed a non-significant tenfold reduction of virus excretion after challenge. Those calves also excreted virus for significantly (p < 0.05) shorter periods (1.5 days) than the non-vaccinated controls. The other constructs encoding gC and VP8 antigens induced no virological protection as compared to controls. Altogether the DNA vaccines induced weaker immunity and protection than conventional marker vaccines tested previously, confirming the difficulty to develop efficient DNA vaccines in large species.     

鸭疫里默氏杆菌多价灭活苗研制的研究报告

用三个血清型的菌株,分别是JYL-1、JYL-2、JYL-7,用两种佐剂,分别是蜂胶和油乳剂共制备了两种多价菌苗,即JYL-1、JYL-2、JYL-7（1、2、7三个血清型）三个RA血清型混合多价蜂胶苗和油乳剂苗。试验结果表明。蜂胶复合佐剂多价苗具有产生免疫保护速度快,免疫持续时间长的优点,接种后第3天即产生部分免疫保护力,第120天时仍具有完全保护力;油乳剂多价苗产生保护力的速度较慢,接种后第10天时开始表现出部分免疫保护,其完全保护力也可持续到接种后第120天。免疫后13d时,免疫保护率可达90％左右。免疫后16d时保护率为100％。免疫后120d时,两种多价菌苗的免疫保护率均可达到100％,免疫后150～180d时,免疫保护率可达800左右。统计学分析证明,菌苗的安全性良好。用3个免疫剂量的菌苗所做的安全试验表明无明显不良反应,菌苗在4℃保存一年,18～22℃室温保存4个月不影响菌苗的免疫效力。田间试验表明,用菌苗免疫鸭群后,可有效地使鸭群抵抗鸭疫里默氏杆菌的感染。     

疫苗免疫在禽病控制上的进展

疫苗免疫已有１０００多年的历史,但只有进入二十世纪以后,疫苗科学才得到了迅速的发展。目前商品性疫苗主要是弱毒活疫苗,灭活疫苗和亚单位疫苗三大类,它们有各自的优点和不足。新一代的疫苗,如基因缺失疫苗,载体疫苗,核酸疫苗和病毒－抗体复合物疫苗等,将从质和量两方面改善其免疫应答和免疫保护,并导致新的疾病控制策略的出现。     

Immunity to toxoplasmosis in hamsters

Protective immunity to Toxoplasma was studied in hamsters. Immunity developed in 2 to 3 weeks after vaccinations were performed. Vaccination with live RH, T-45, and ts-4 strains afforded the best protection against challenge exposure with the most pathogenic RH strain used. Even a killed-toxoplasma vaccine protected all hamsters against the slightly less pathogenic T-1 strain through 24 weeks, but it did not protect hamsters against challenge exposure with the RH strain. Both ts-4, a nonpersistent strain, and killed-toxoplasma vaccine provided protective immunity in hamsters that was not dependent upon premunition. Toxoplasma antibody titers in hamsters given the 2 vaccines were similar. However, there was a difference in the quality of immunity: fever and body weight loss were seen in hamsters vaccinated with the killed-toxoplasma vaccine after they were challenge exposed with T-1 strain, whereas these changes were rarely seen in hamsters given the live-toxoplasma vaccine and then challenge exposed with RH strain. Delayed-type hypersensitivity to Toxoplasma antigen always appeared before protective immunity and was detected in all hamsters by 4 days after vaccination with live-toxoplasma strains. Although the development of delayed-type hypersensitivity preceded protective immunity, it was not indicative that protective immunity was present or would develop.     

Current perspectives on control of equine influenza

Influenza A viruses of the H3N8 subtype are a major cause of respiratory disease in horses. Subclinical infection with virus shedding can occur in vaccinated horses, particularly where there is a mismatch between the vaccine strains and the virus strains circulating in the field. Such infections contribute to the spread of the disease. Rapid diagnostic techniques are available for detection of virus antigen and can be used as an aid in control programmes. Improvements have been made to methods of standardising inactivated virus vaccines, and a direct relationship between vaccine potency measured by single radial diffusion and vaccine-induced antibody measured by single radial haemolysis has been demonstrated. Improved adjuvants and antigenic presentation systems extend the duration of immunity induced by inactivated virus vaccines, but high levels of antibody are required for protection against field infection. In addition to circulating antibody, infection with influenza virus stimulates mucosal and cellular immunity; unlike immunity to inactivated virus vaccines, infection-induced immunity is not dependent on the presence of circulating antibody to HA. Live attenuated or vectored equine influenza vaccines, which may better mimic the immunity generated by influenza infection than inactivated virus vaccines, are now available. Mathematical modelling based upon experimental and field data has been applied to examine issues relating to vaccine efficacy at the population level. A vaccine strain selection system has been implemented and a more global approach to the surveillance of equine influenza is being developed.     

Overview of new vaccines and technologies

Molecular technology has given us a greater insight into the aetiology of disease, the functioning of the immune system and the mode of action of veterinary pathogens. The knowledge gained has been used to develop new vaccines with specific, reactive antigens which elicit protective immune mediated responses (humoral and/or cell mediated) in the host. These vaccines should not burden the immune system by initiating responses against non-essential antigens. However, the efficacy of these vaccines is only as good as the delivery technology or route used to present them to the immune system. Some vaccines, traditionally given by the parenteral route, are now given by the natural route; either orally or intranasally. Two major advantages, often interrelated, are the rapid onset of immunity and stimulation of the local, mucosal immunity. These new technologies are now making an impact on current vaccine development. The balance has to be found between what is technologically feasible and what will provide at least as good a protective immunity as current, conventional vaccines. As new and emerging diseases appear globally, new opportunities arise for molecular and conventional technologies to be applied to both the development and delivery of novel vaccines, as well as the improvement of vaccines in current use.     

Recent advances in immunomodulation and vaccination strategies against coccidiosis

Coccidiosis is a ubiquitous intestinal protozoan infection of poultry seriously impairing the growth and feed utilization of infected animals. Conventional disease control strategies rely heavily on chemoprophylaxis, which is a tremendous cost to the industry. Existing vaccines consist of live virulent or attenuated Eimeria strains with limited scope of protection against an ever-evolving and widespread pathogen. The continual emergence of drug-resistant strains of Eimeria, coupled with the increasing regulations and bans on the use of anticoccidial drugs in commercial poultry production, urges the need for novel approaches and alternative control strategies. Because of the complexity of the host immunity and the parasite life cycle, a comprehensive understanding of host-parasite interactions and protective immune mechanisms becomes necessary for successful prevention and control practices. Recent progress in functional genomics technology would facilitate the identification and characterization of host genes involved in immune responses as well as parasite genes and proteins that elicit protective host responses. This study reviews recent coccidiosis research and provides information on host immunity, immunomodulation, and the latest advances in live and recombinant vaccine development against coccidiosis. Such information will help magnify our understanding of host-parasite biology and mucosal immunology, and we hope it will lead to comprehensive designs of nutritional interventions and vaccination strategies for coccidiosis.