Influenza vaccines and vaccination strategies in birds

Although it is well accepted that the present Asian H5N1 panzootic is predominantly an animal health problem, the human health implications and the risk of human pandemic have highlighted the need for more information and collaboration in the field of veterinary and human health. H5 and H7 avian influenza (AI) viruses have the unique property of becoming highly pathogenic (HPAI) during circulation in poultry. Therefore, the final objective of poultry vaccination against AI must be eradication of the virus and the disease. Actually, important differences exist in the control of avian and human influenza viruses. Firstly, unlike human vaccines that must be adapted to the circulating strain to provide adequate protection, avian influenza vaccination provides broader protection against HPAI viruses. Secondly, although clinical protection is the primary goal of human vaccines, poultry vaccination must also stop transmission to achieve efficient control of the disease. This paper addresses these differences by reviewing the current and future influenza vaccines and vaccination strategies in birds.     

Efficacy of vaccines in chickens against highly pathogenic Hong Kong H5N1 avian influenza.

In 1997, highly pathogenic (HP) H5N1 avian influenza virus (AIV) caused infections in poultry in Hong Kong and crossed into humans, resulting in a limited number of infections including 18 hospitalized cases and six associated deaths. The unique ability of this, AIV to infect both poultry and people raised a concern for the potential of humans to be biological as well as mechanical vectors of this AIV to poultry. The current study was undertaken to determine if existing vaccines and their technologies could be used during an outbreak to protect poultry. Commercial and experimental inactivated whole H5 AIV and baculovirus-expressed AIV H5 hemagglurinin protein vaccines provided protection from clinical signs and death in chickens after lethal challenge by human-origin HP H5N1 Hong Kong strains 156/97 and 483/97. The commercial and experimental inactivated vaccines had mean protective doses ranging from 0.25 to 0.89, which represents the milligrams of viral protein in the vaccines that provided protection from death in half of the birds. Furthermore, the vaccines reduced the ability of the challenge AIV to replicate in chickens and decreased the recovery of challenge AIV from the enteric and respiratory tracts, but the use of a vaccine will nor totally prevent AI virus replication and shedding. Existing vaccines will protect poultry from mortality and reduce virus replication from the new HP AIV strain that can infect both poultry and humans.     

Recent developments in avian influenza research: epidemiology and immunoprophylaxis

Influenza A viruses have been isolated from humans, from several other mammalian species and a wide variety of avian species, among which, wild aquatic birds represent the natural hosts of influenza viruses. The majority of the possible combinations of the 15 haemagglutinin (HA) and nine neuraminidase (NA) subtypes recognized have been identified in isolates from domestic and wild birds. Infection of birds can cause a wide range of clinical signs, which may vary according to the host, the virus strain, the host's immune status, the presence of any secondary exacerbating microorganisms and environmental factors. Most infections are inapparent, especially in waterfowl and other wild birds. In contrast, infections caused by viruses of H5 and H7 subtypes can be responsible for devastating epidemics in poultry. Despite the warnings to the poultry industry about these viruses, in 1997 an avian H5N1 influenza virus was directly transmitted from birds to humans in Hong Kong and resulted in 18 confirmed infections, thus strengthening the pandemic threat posed by avian influenza (AI). Indeed, reassortant viruses, harbouring a combination of avian and human viral genomes, have been responsible for major pandemics of human influenza. These considerations warrant the need to continue and broaden efforts in the surveillance of AI. Control programmes have varied from no intervention, as in the case of the occurrence of low pathogenic (LP) AI (LPAI) viruses, to extreme, expensive total quarantine-slaughter programmes carried out to eradicate highly pathogenic (HP) AI (HPAI) viruses. The adoption of a vaccination policy, targeted either to control or to prevent infection in poultry, is generally banned or discouraged. Nevertheless, the need to boost eradication efforts in order to limit further spread of infection and avoid heavy economic losses, and advances in modern vaccine technologies, have prompted a re-evaluation of the potential use of vaccination in poultry as an additional tool in comprehensive disease control strategies. This review presents a synthesis of the most recent research on AI that has contributed to a better understanding of the ecology of the virus and to the development of safe and efficacious vaccines for poultry.     

广西玉林市规模化禽场禽流感病毒检测

为了解广西玉林市2020年规模禽场禽流感病毒感染状况,采用荧光RT-PCR方法,对广西玉林市7个县(市、区)42个规模化禽场采集的1260份禽喉/泄殖腔棉拭子样品进行了通用型禽流感病毒核酸检测(荧光PCR),并对检测为阳性的样本进行H5、H7亚型(双重荧光PCR)和H9亚型(荧光PCR)分型鉴定.结果显示:在42个规模...     

Improvements to the hemagglutination inhibition test for serological assessment of recombinant fowlpox-H5-avian-influenza vaccination in chickens and its use along with an agar gel immunodiffusion test for differentiating infected from noninfected vaccinated animals

In general, avian influenza (AI) vaccines protect chickens from morbidity and mortality and reduce, but do not completely prevent, replication of wild AI viruses in the respiratory and intestinal tracts of vaccinated chickens. Therefore, surveillance programs based on serological testing must be developed to differentiate vaccinated flocks infected with wild strains of AI virus from noninfected vaccinated flocks in order to evaluate the success of vaccination in a control program and allow continuation of national and international commerce of poultry and poultry products. In this study, chickens were immunized with a commercial recombinant fowlpox virus vaccine containing an H5 hemagglutinin gene from A/turkey/Ireland/83 (H5N8) avian influenza (AI) virus (rFP-H5) and evaluated for correlation of immunological response by hemagglutination inhibition (HI) or agar gel immunodiffusion (AGID) tests and determination of protection following challenge with a high pathogenicity AI (HPAI) virus. In two different trials, chickens immunized with the rFP-H5 vaccine did not develop AGID antibodies because the vaccine lacks AI nucleoprotein and matrix genes, but 0%-100% had HI antibodies, depending on the AI virus strain used in the HI test, the HI antigen inactivation procedure, and whether the birds had been preimmunized against fowlpox virus. The most consistent and highest HI titers were observed when using A/turkey/Ireland/83 (H5N8) HPAI virus strain as the beta-propiolactone (BPL)-inactivated HI test antigen, which matched the hemagglutinin gene insert in the rFP-H5 vaccine. In addition, higher HI titers were observed if ether or a combination of ether and BPL-inactivated virus was used in place of the BPL-inactivated virus. The rFP-H5 vaccinated chickens survived HPAI challenge and antibodies were detected by both AGID and HI tests. In conclusion, we demonstrated that the rFP-H5 vaccine allowed easy serological differentiation of infected from noninfected birds in vaccinated populations of chickens when using standard AGID and HI tests.     

Avian influenza vaccines and therapies for poultry

Vaccines have been used in avian influenza (AI) control programs to prevent, manage or eradicate AI from poultry and other birds. The best protection is produced from the humoral response against the hemagglutinin (HA) protein. A variety of vaccines have been developed and tested under experimental conditions with a few receiving licensure and field use following demonstration of purity, safety, efficacy and potency. Current licensed vaccines are predominately inactivated whole AI vaccines, typically produced from low pathogenicity (LP) AI virus strains, or occasionally from high pathogenicity AI virus strains. Recently, reverse genetic procedures have been developed that allow construction of vaccine strains using a genetically altered HA gene (changing HP HA proteolytic cleavage site to LP) and a backbone of internal gene segments for safe, high growth production. Other licensed AI vaccines include recombinant fowl poxvirus vector with an AI H5 insert and a recombinant Newcastle disease virus vector with an AI H5 gene insert. The latter vaccine can be mass administered via aerosol application.     

Immunogenicity and efficacy of fowlpox-vectored and inactivated avian influenza vaccines alone or in a prime-boost schedule in chickens with maternal antibodies

Inactivated and fowlpox virus (FP)-vectored vaccines have been used to control H5 avian influenza (AI) in poultry. In H5 AI endemic countries, breeder flocks are vaccinated and therefore, maternally-derived antibodies (MDA) are transferred to their progeny. Results of three immunogenicity and one efficacy studies performed in birds with or without MDA indicated that the immunogenicity of an inactivated vaccine based on a H5N9 AI isolate (inH5N9) was severely impaired in chicks hatched from inH5N9-vaccinated breeders. This MDA interference was lower when breeders received only one administration of the same vaccine and could be overcome by priming the chicks at day-of-age with a live recombinant FP-vectored vaccine with H5 avian influenza gene insert (FP-AI). The interference of anti-FP MDA was of lower intensity than the interference of anti-AI MDA. The highest interference observed on the prime-boost immunogenicity was in chicks hatched from breeders vaccinated with the same prime-boost scheme. The level of protection against an antigenic variant H5N1 highly pathogenic AI isolate from Indonesia against which the FP-AI or inH5N9 alone was poorly protective could be circumvented by the prime-boost regimen in birds with either FP or AI MDA. Thus, the immunogenicity of vaccines in young chicks with MDA depends on the vaccination scheme and the type of vaccine used in their parent flocks. The heterologous prime-boost in birds with MDA may at least partially overcome MDA interference on inactivated vaccine.     

Chinese poultry farmers' decision‐making for avian influenza prevention: a qualitative analysis

Poultry farmers faced dual risk when mutant avian influenza (AI) virus showed the zoonotic characteristics. A/H5N1 and A/H7N9 were two dominant AI virus strains that have captured the attention of the public over the years for they have been reported to bring about greater loss to poultry and human, respectively. Previous studies mainly used quantitative methods investigating either the means that poultry farmers adopted for protecting their poultry against A/H5N1 infection or the poultry farmers' self‐protective behaviours against A/H7N9 infection. We sought insights into the underlying factors influencing Chinese poultry farmers' protective behaviours in response to the dual risk of AI by a qualitative way. Semi‐structured in‐depth interviews were conducted with 25 Chinese chicken farmers recruited by purposive sampling between November 2016 and May 2017, the peak season of AI. All interviews were audio‐taped, transcribed and analysed using a grounded theory approach. From participants' experiences, we revealed five main themes: Measures adopted for protecting poultry and farmers, Emotional response to the AI epidemic, Perceived risk of AI, Perceived effectiveness of the preventive measures adopted and Perceived self‐efficacy to take preventive measures. The information of AI outbreak directly triggered Chinese chicken farmers' emotional response and thereafter preventive actions. Compared to the perceived risk of poultry infection with A/H5N1 which mainly connected to economic loss, participants perceived much lower risk of human infection with A/H7N9. AI epidemic information played a key role triggering poultry farmers' response behaviours. Chinese poultry farmers weighted more attention on the risk of poultry infection which was highly associated with economic losses. The government should build and improve an early AI warning and information transmission network to poultry farmers. Further reinforcement of related self‐protective and preventive knowledge training towards poultry farmers is necessary.     

Public health risk from avian influenza viruses

Since 1997, avian influenza (AI) virus infections in poultry have taken on new significance, with increasing numbers of cases involving bird-to-human transmission and the resulting production of clinically severe and fatal human infections. Such human infections have been sporadic and are caused by H7N7 and H5N1 high-pathogenicity (HP) and H9N2 low-pathogenicity (LP) AI viruses in Europe and Asia. These infections have raised the level of concern by human health agencies for the potential reassortment of influenza virus genes and generation of the next human pandemic influenza A virus. The presence of endemic infections by H5N1 HPAI viruses in poultry in several Asian countries indicates that these viruses will continue to contaminate the environment and be an exposure risk with human transmission and infection. Furthermore, the reports of mammalian infections with H5N1 AI viruses and, in particular, mammal-to-mammal transmission in humans and tigers are unprecedented. However, the subsequent risk for generating a pandemic human strain is unknown. More international funding from both human and animal health agencies for diagnosis or detection and control of AI in Asia is needed. Additional funding for research is needed to understand why and how these AI viruses infect humans and what pandemic risks they pose.     

Induction of respiratory immune responses in the chicken; implications for development of mucosal avian influenza virus vaccines

The risk and the size of an outbreak of avian influenza virus (AIV) could be restricted by vaccination of poultry. A vaccine used for rapid intervention during an AIV outbreak should be safe, highly effective after a single administration and suitable for mass application. In the case of AIV, aerosol vaccination using live virus is not desirable because of its zoonotic potential and because of the risk for virus reassortment. The rational design of novel mucosal-inactivated vaccines against AIV requires a comprehensive knowledge of the structure and function of the lung-associated immune system in birds in order to target vaccines appropriately and to design efficient mucosal adjuvants. This review addresses our current understanding of the induction of respiratory immune responses in the chicken. Furthermore, possible mucosal vaccination strategies for AIV are highlighted.     

Research Progress on Novel Vaccine of Avian Influenza

Avian influenza (AI) is an acute respiratory disease caused by influenza A virus.Avian influenza virus (AIV) can infect poultry,wild birds and some mammals including human.AI is a big threat to both poultry and human health because the virus can cross the species barrier to get the capacity of transmitting from poultry to human.Vaccination is the most efficient measure against AI outbreaking.Traditional vaccines include inactivated vaccine based on chick embryo and attenuated vaccine.Although the traditional vaccines play important roles in the past AI epidemics,many disadvantages have been proved to exist in traditional vaccines.Forced by major drawbacks of traditional vaccines,several studies focused on the development of novel vaccines.In this review,we reviewed recombinant live vector vaccine,subunit vaccine,DNA vaccine and virus-like particle vaccine of AI in order to provide some references for prevention and control of AI.     

禽流感新型疫苗研究进展

禽流感是由A型流感病毒引起的一种急性呼吸道传染病,家禽、野鸟和部分哺乳动物均可感染.禽流感给中国养殖业造成了巨大的损失,同时,随着病毒的种间传播,人类的生命安全也受到了严重威胁.目前,疫苗免疫仍是防控禽流感最主要的手段,传统的疫苗主要有鸡胚灭活苗和禽流感弱毒疫苗.虽然在过往几次禽流感暴发过程中,传统疫苗发挥了重要作用,但其自身却存在诸多弊端,因此研制新型疫苗来弥补传统疫苗的不足是很有必要的.文章主要对禽流感重组活载体疫苗、基因工程亚单位疫苗、DNA疫苗和病毒样颗粒疫苗等新型疫苗的研究进展进行综述,旨在为禽流感的防控提供参考.     

Vaccines protect chickens against H5 highly pathogenic avian influenza in the face of genetic changes in field viruses over multiple years

Inactivated whole avian influenza (AI) virus vaccines, baculovirus-derived AI haemagglutinin vaccine and recombinant fowlpoxvirus-AI haemagglutinin vaccine were tested for the ability to protect chickens against multiple highly pathogenic (HP) H5 AI viruses. The vaccine and challenge viruses, or their haemagglutinin protein components, were obtained from field AI viruses of diverse backgrounds and included strains obtained from four continents, six host species, and isolated over a 38-year-period. The vaccines protected against clinical signs and death, and reduced the number of chickens shedding virus and the titre of the virus shed following a HP H5 AI virus challenge. Immunization with these vaccines should decrease AI virus shedding from the respiratory and digestive tracts of AI virus exposed chickens and reduce bird-to-bird transmission. Although most consistent reduction in respiratory shedding was afforded when vaccine was more similar to the challenge virus, the genetic drift of avian influenza virus did not interfere with general protection as has been reported for human influenza viruses.     

A lack of antibody formation against inactivated influenza virus after aerosol vaccination in presence or absence of adjuvantia

In the poultry industry, infections with avian influenza virus (AIV) can result in significant economic losses. The risk and the size of an outbreak might be restricted by vaccination of poultry. A vaccine that would be used for rapid intervention during an outbreak should be safe to use, highly effective after a single administration and be suitable for mass application. A vaccine that could be applied by spray or aerosol would be suitable for mass application, but respiratory applied inactivated influenza is poorly immunogenic and needs to be adjuvanted. We chose aluminum OH, chitosan, cholera toxin B subunit (CT-B), and Stimune as adjuvant for an aerosolized vaccine with inactivated H9N2. Each adjuvant was tested in two doses. None of the adjuvanted vaccines induced AIV-specific antibodies after single vaccination, measured 1 and 3 weeks after vaccination by aerosol, in contrast to the intramuscularly applied vaccine. The aerosolized vaccine did enter the chickens' respiratory tract as CT-B-specific serum antibodies were detected after 1 week in chickens vaccinated with the CT-B-adjuvanted vaccine. Chickens showed no adverse effects after the aerosol vaccination based on weight gain and clinical signs. The failure to detect AIV-specific antibodies might be due to the concentration of the inactivated virus.     

Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates

Beginning in April 2009, a novel H1N1 influenza virus caused acute respiratory disease in humans, first in Mexico and then around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June 2009 and later in breeder turkeys in Chile, Canada, and the United States. The pH1N1 virus consists of gene segments of avian, human, and swine influenza origin and has the potential for infection in poultry following exposure to infected humans or swine. We examined the clinical events following the initial outbreak of pH1N1 in turkeys and determined the relatedness of the hemagglutinin (HA) gene segments from the pH1N1 to two H1N1 avian influenza (AI) isolates used in commercial turkey inactivated vaccines. Overall, infection of turkey breeder hens with pH1N1 resulted in -50% reduction of egg production over 3-4 weeks. Genetic analysis indicated one H1N1 AI vaccine isolate (Alturkey/North Carolina/17026/1988) contained approximately 92% nucleotide sequence similarity to the pH1N1 virus (A/Mexico/4109/2009); whereas, a more recent AI vaccine isolate (A/ swine/North Carolina/00573/2005) contained 75.9% similarity. Comparison of amino acids found at antigenic sites of the HA protein indicated conserved epitopes at the Sa site; however, major differences were found at the Ca2 site between pH1N1 and A/ turkey/North Carolina/127026/1988. Hemagglutinin-inhibition (HI) tests were conducted with sera produced in vaccinated turkeys in North Carolina to determine if protection would be conferred using U.S. AI vaccine isolates. HI results indicate positive reactivity (HI titer > or = 5 log2) against the vaccine viruses over the course of study. However, limited cross-reactivity to the 2009 pH1N1 virus was observed, with positive titers in a limited number of birds (6 out of 20) beginning only after a third vaccination. Taken together, these results demonstrate that turkeys treated with these vaccines would likely not be protected against pH1N1 and current vaccines used in breeder turkeys in the United States against circulating H1N1 viruses should be updated to ensure adequate protection against field exposure.     

Modelling influenza A H5N1 vaccination strategy scenarios in the household poultry sector in Egypt

Highly pathogenic avian influenza (AI) due to H5N1 virus was first reported in Egypt in February 2006; since then, the government has allowed avian influenza vaccination in poultry. The present study evaluated the impact of AI vaccination in terms of cumulative annual flock immunity (CAFI): the percentage of bird × weeks protected by immunity. This evaluation took account of the combined effects of vaccination coverage, vaccine efficacy (VE), and different characteristics of household poultry production on the effectiveness of the adopted vaccination strategy (VS), and provided alternative options for improvement. The evaluation used a population and vaccination model that calculates the CAFI. Participatory approaches were employed in 21 villages to develop the vaccination and flock parameters required for the model. The adopted VS were compared in the model with three alternative VS scenarios in terms of the CAFI. Vaccination coverage varied among villages but was generally low (between 1 and 48 %; median 14 %). Under the adopted VS, the CAFI predicted for the villages ranged from 2 to 31 %. It was concluded that despite the enormous effort put into rural household poultry AI vaccination by the Egyptian government, village CAFI is unlikely to be maintained at the levels required to significantly reduce the virus load and restrict transmission. In HPAI-endemic countries that consider AI vaccination as one of the disease control options, the high cost of mass AI vaccination campaigns and their achievable benefits must be compared with other available control measures, which may include targeted vaccination. Achievable vaccination coverage, VE and the different characteristics of commercial and household (village) poultry production are key parameters determining the feasibility and cost-effectiveness of different AI vaccination strategies.     

禽流感免疫预防的探讨

近年来,在禽流感新型疫苗研究上取得了一定进展,但是目前国内外禽流感免疫仍主要使用灭活疫苗.大量的研究和防控实践表明,有效的禽流感疫苗接种可预防家禽发病,阻断病毒的传播,即使免疫禽受到强毒攻击感染后病毒排出量也显著减少,这就减少了病毒发生自然突变的机会,降低了疫病向禽群和人传播的风险;疫苗的正确应用可在控制禽流感中发挥重要作用.因此,应根据不同地区总体防控策略和具体疫情状况,正确评估禽流感免疫预防作用.在禽流感发生的高风险地区,全面预防接种是防控禽流感的关键技术措施,具有至关重要的作用.     

Comparative susceptibility of chickens and turkeys to avian influenza A H7N2 virus infection and protective efficacy of a commercial avian influenza H7N2 virus vaccine

During the spring of 2002, a low pathogenic avian influenza (LPAI) A (H7N2) virus caused a major outbreak among commercial poultry in Virginia and adjacent states. The virus primarily affected turkey flocks, causing respiratory distress and decreased egg production. Experimentally, turkeys were more susceptible than chickens to H7N2 virus infection, with 50% bird infectious dose titers equal to 10(0.8) and 10(2.8-3.2), respectively. Comparison of virus shedding from the cloaca and oropharynx demonstrated that recent H7N2 virus isolates were readily isolated from the upper respiratory tract but rarely from the gastrointestinal tract. The outbreak of H7N2 virus raised concerns regarding the availability of vaccines that could be used for the prevention and control of this virus in poultry. We sought to determine if an existing commercial avian influenza (AI) vaccine prepared from a 1997 seed stock virus could provide protection against a 2002 LPAI H7N2 virus isolated from a turkey (A/turkey/Virginia/158512/02 [TV/02]) in Virginia that was from the same lineage as the vaccine virus. The inactivated AI vaccine, prepared from A/chicken/ Pennsylvania/21342/97 (CP/97) virus, significantly reduced viral shedding from vaccinated turkeys in comparison with sham controls but did not prevent infection. The protective effect of vaccination correlated with the level of virus-specific antibody because a second dose of vaccine increased antiviral serum immunoglobulin G and hemagglutination inhibition (HI) reactivity titers in two different turkey age groups. Serum from CP/97-vaccinated turkeys reacted equally well to CP/97 and TV/02 antigens by HI and enzyme-linked immunosorbent assay. These results demonstrate the potential benefit of using an antigenically related 1997 H7N2 virus as a vaccine candidate for protection in poultry against a H7N2 virus isolate from 2002.     

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.     

Recent developments in fish vaccinology

During the last 10 to 20 years vaccination has become established as an important method for prevention of infectious diseases in farmed fish, mainly salmonid species. So far, most commercial vaccines have been inactivated vaccines administered by injection or immersion. Bacterial infections caused by Gram-negative bacteria such as Vibrio sp., Aeromonas sp., and Yersinia sp. have been effectively controlled by vaccination. With furunculosis, the success is attributed to the use of injectable vaccines containing adjuvants. Vaccines against virus infections, including infectious pancreatic necrosis, have also been used in commercial fish farming. Vaccines against several other bacterial and viral infections have been studied and found to be technically feasible. Pasteurellosis, streptococcosis (lactococcosis) and infections with iridoviruses are candidate diseases for control by immunoprophylaxis in the near future. The overall positive effect of vaccination in farmed fish is reduced mortality. However, for the future of the fish farming industry it is also important that vaccination contributes to a sustainable biological production with negligible consumption of antibiotics. A potential side-effect associated with injectable vaccines is local reactions in the peritoneal cavity. The paper presents recent developments in immunoprophylaxis of fish and some problems that should be addressed by the research community in the years to come.