RESUMEN
This paper describes those components of governance and management of a public veterinary laboratory that are deemed essential for the effective delivery of a diagnostic service. Whilst broadly applicable to all veterinary diagnostic services, there is a focus on publicly supported veterinary diagnostic laboratories in developing countries, highlighting the critical components that should be established as a minimum. The need for establishing overarching ownership, governance and resourcing is emphasised but followed by a detailed account of the components of diagnostic service management and delivery, linked to a description of the key support services that are essential in assisting delivery. Elements of quality assurance and compliance are described, with an emphasis on the need to both understand and meet the regulatory environment in which a diagnostic laboratory now operates. The outputs from a veterinary laboratory must be rooted in sound science, and mechanisms must be in place to prevent corrupt practices and inappropriate political influences.
Asunto(s)
Enfermedades de los Animales/diagnóstico , Servicios de Laboratorio Clínico/organización & administración , Servicios de Laboratorio Clínico/normas , Medicina Veterinaria/normas , Bienestar del Animal , Animales , Servicios de Laboratorio Clínico/economía , Sector Privado , Sector Público , Control de Calidad , Administración de la SeguridadRESUMEN
In August 2007 Australia experienced its first outbreak of equine influenza. The disease occurred first in a quarantine station for imported horses near Sydney and subsequently escaped into the general horse population. After an extensive campaign the disease was eradicated and Australia is again recognised as free of this disease. Equine influenza was then, and is now, recognised to be the major disease risk associated with live horse imports into Australia and measures designed to mitigate this risk formed the basis of the quarantine protocols then in place. Subsequent investigations into the cause of the outbreak identified failures in compliance with these quarantine requirements as a contributing factor. It is also likely that the immunity of horses vaccinated as part of the import protocol was less than optimal, and that this had a significant role to play in the escape of the disease from quarantine.
Asunto(s)
Brotes de Enfermedades/veterinaria , Enfermedades de los Caballos/epidemiología , Subtipo H3N8 del Virus de la Influenza A , Infecciones por Orthomyxoviridae/veterinaria , Cuarentena/normas , Animales , Australia/epidemiología , Comercio/legislación & jurisprudencia , Comercio/normas , Brotes de Enfermedades/prevención & control , Enfermedades de los Caballos/prevención & control , Caballos , Subtipo H3N8 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/prevención & control , Cuarentena/legislación & jurisprudencia , Vacunación/legislación & jurisprudencia , Vacunación/normas , Vacunación/veterinariaRESUMEN
In August 2007, several horses showed pyrexia and respiratory signs while in post-arrival quarantine in Australia. Subsequent investigations diagnosed equine influenza by serology and PCR in two quarantine stations. A common origin in a shipment of horses from Japan was indicated.
Asunto(s)
Enfermedades de los Caballos/virología , Subtipo H3N8 del Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/veterinaria , Animales , Anticuerpos Antivirales/sangre , Australia/epidemiología , Pruebas de Inhibición de Hemaglutinación/veterinaria , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/epidemiología , Caballos , Subtipo H3N8 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/sangre , Infecciones por Orthomyxoviridae/virología , Cuarentena/veterinaria , ARN Viral/química , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinariaRESUMEN
Before 2007, equine influenza had never been diagnosed in Australia. On 22 August 2007, infection was confirmed in horses at Eastern Creek Animal Quarantine Station near Sydney. The virus subsequently isolated (A/equine/Sydney/2888-8/2007) was confirmed by sequence analysis of the haemagglutinin (HA) gene as an H3 virus of the variant American Florida lineage that is now referred to as Clade 1. The HA sequence of the virus was identical to that of a virus isolated from a contemporaneous outbreak in Japan and showed high homology to viruses circulating in North America.
Asunto(s)
Enfermedades de los Caballos/virología , Subtipo H3N8 del Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/virología , Animales , Australia , Hemaglutininas/genética , Enfermedades de los Caballos/genética , Caballos , Subtipo H3N8 del Virus de la Influenza A/genética , América del Norte , Infecciones por Orthomyxoviridae/genética , Filogenia , ARN Viral/química , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Análisis de Secuencia de ADNRESUMEN
An outbreak of H3N8 Equine Influenza virus (EIV) that occurred in vaccinated horses in Japan was caused by a genetically divergent EIV isolate of the Florida clade 1 sub-lineage. This virus subsequently entered Australia where it infected thousands of immunologically naïve horses. The objective of this study was to evaluate the ability of a non-updated whole inactivated equine influenza (EI) vaccine to protect if used in the face of an outbreak induced by a virus similar to the ones circulating in Japan and Australia in 2007. Seven naïve Welsh mountain ponies were immunised twice with the commercially available vaccine Duvaxyn IE-T Plus and experimentally infected with A/eq2/Sydney/2888-8/07. Five ponies remained unvaccinated as controls. The ponies were challenged in an ACDP (Advisory Committee on Dangerous Pathogens) Category III containment facility by exposure to a nebulised aerosol of A/eq2/Sydney/2888-8/07 two weeks after the second vaccination. Clinical signs and virus shedding were monitored for 14 days post-challenge infection. After challenge infection, all control ponies developed clinical signs of disease with coughing being particularly noteworthy when compared with vaccinated ponies. Only 3 out of 5 controls developed pyrexia for up to 3 days, and 1 out of 7 vaccinates was pyretic for 1 day. Nasal discharge was evident in both control and vaccinated ponies with no significant difference between groups. Three different methods were used to measure virus shedding in nasal secretions (i.e. titration in embryonated hens' eggs, EIV NP ELISA and EIV NP qRT-PCR). The intensity and duration of EIV shedding significantly decreased in the vaccinated group when compared with the control ponies. All control ponies seroconverted after experimental infection with A/eq2/Sydney/2888-8/07 whereas only 1 out of 7 vaccinated ponies had a significant increase in antibody. Duvaxyn IE-T Plus therefore reduced clinical signs and virus shedding when ponies were challenged with A/eq2/Sydney/2888-8/07 (H3N8), 2 weeks after a second dose of vaccine.
Asunto(s)
Brotes de Enfermedades/veterinaria , Enfermedades de los Caballos/virología , Subtipo H3N8 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/veterinaria , Vacunación/veterinaria , Animales , Anticuerpos Antivirales/sangre , Australia/epidemiología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/inmunología , Caballos , Subtipo H3N8 del Virus de la Influenza A/genética , Vacunas contra la Influenza/normas , Japón/epidemiología , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , ARN Viral/química , ARN Viral/genética , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Vacunación/métodos , Vacunación/normas , Vacunas de Productos Inactivados/inmunología , Esparcimiento de Virus/inmunologíaRESUMEN
Since the 1980s, a number of key events have significantly altered our ideas on biosecurity and the role of biocontainment laboratories, such as the bovine spongiform encephalopathy (BSE) and severe acute respiratory syndrome (SARS) outbreaks and the anthrax episode of 2001 in the USA. This has resulted in the development of plans to build "high containment" facilities around the world and an array of new regulations at both national and international levels regarding the management of pathogens, the operation of high containment facilities, the use of genetically modified material, and the transportation of such agents and personnel security issues. Considering the cost, however, it is debatable whether every country needs to build its own high containment facility. The Australian Animal Health Laboratory (AAHL) provides an example of what might be considered best practice in biocontainment while considering regulations, cost and need.
Asunto(s)
Contención de Riesgos Biológicos/tendencias , Medidas de Seguridad/tendencias , Animales , Australia , Contención de Riesgos Biológicos/veterinaria , Humanos , Laboratorios , SeguridadRESUMEN
This paper describes an objective system of monitoring the performance of disease surveillance. The system was developed through dialogue with a number of countries in Africa and adopted as part of the Global Rinderpest Eradication Programme of the Food and Agriculture Organization of the United Nations. The performance monitoring system uses a clinical stomatitis-enteritis case definition, an outbreak investigation classification scheme, and a series of eight performance indicators to measure the sensitivity, specificity and timeliness of the surveillance system. Field-testing indicates that the approach is successful when good record-keeping is practiced and highlights the importance of dialogue in helping to ensure that the system is simple and acceptable. The system provides a quantitative measure of the efficacy of national disease surveillance programmes and of the quality of data derived from such programmes for use in international disease control, animal health information exchange and trade risk analysis.
Asunto(s)
Control de Enfermedades Transmisibles/normas , Peste Bovina/prevención & control , Animales , Control de Enfermedades Transmisibles/métodos , Brotes de Enfermedades/estadística & datos numéricos , Brotes de Enfermedades/veterinaria , Enteritis/epidemiología , Enteritis/veterinaria , Salud Global , Vigilancia de la Población , Peste Bovina/epidemiología , Sensibilidad y Especificidad , Estomatitis/epidemiología , Estomatitis/veterinariaRESUMEN
During the past thirteen years, and as part of an overall support program for developing countries, the Joint FAO/IAEA Division has developed a series of standardized and internationally validated ELISA-based systems for the diagnosis and surveillance of the major epizootics affecting livestock in the developing world. Linked to comprehensive internal and external quality assurance protocols and to the use of standardized equipment and data management software, veterinary laboratories in many developing countries are now able to provide quality assured results on the prevalence of the major diseases affecting their livestock. This internationally standardized approach can rapidly enable developing countries to both monitor the effectiveness of their disease control and eradication programs and to meet requirements for international disease status recognition and for trade in livestock and livestock products.
Asunto(s)
Enfermedades de los Animales/diagnóstico , Técnicas de Laboratorio Clínico/veterinaria , Cooperación Internacional , Enfermedades de los Animales/epidemiología , Enfermedades de los Animales/prevención & control , Crianza de Animales Domésticos , Animales , Animales Domésticos , Ensayo de Inmunoadsorción Enzimática , Juego de Reactivos para Diagnóstico/veterinaria , Reproducibilidad de los ResultadosRESUMEN
The problems facing veterinary diagnostic laboratories in developing countries range from simple problems, such as limited funds to keep good personnel or obtain equipment, supplies, reagents or training, to the more complex problems of designing and executing appropriate sample collection schemes for disease surveillance of evaluating the performance characteristics of a new diagnostic assay. While many developing countries are addressing these problems independently and a number of international and national organisations provide various forms of external support, the Office International des Epizooties (OIE) must continue in its critical role to provide guidelines for the most appropriate diagnostic assays for trade purposes and the development of the primary reference reagents for these assays. In addition, the OIE should take the lead in development of quality management guidelines for veterinary diagnostic testing laboratories. Without these guidelines and standards, diagnostic laboratories in developing countries will have difficulty in gaining the credibility necessary to help improve the positions of their countries in the international trade of livestock and livestock commodities.
Asunto(s)
Enfermedades de los Animales/diagnóstico , Técnicas de Laboratorio Clínico/normas , Países en Desarrollo , Laboratorios/normas , Medicina Veterinaria , Animales , Animales Domésticos , Comercio , Laboratorios/economía , Personal de Laboratorio Clínico/educación , Personal de Laboratorio Clínico/normas , Control de Calidad , Estándares de ReferenciaRESUMEN
Reference standards are used to calibrate similar assay systems against an international reference protocol and to provide a template for the preparation of secondary and/or working standards. Three reference standards are recommended for the indirect enzyme-linked immunosorbent assay: a strong positive standard, a weak positive standard and a negative serum standard. The negative standard should be derived from a single serum or from a serum pool which exhibits typical background activity in the reference protocol. The strong and weak positive standards should be derived from a single serum or from a serum pool which typifies the humoral response (antibody) to natural infection. Suitable candidates for the positive reference standards should exhibit dose/response curves in the mid-range of antibody activity. The strong and weak positive standards should each be prepared from a one-time dilution in the negative standard, to yield antibody activities which are defined by specific points on the linear portion of the dose/response curve. The strong positive standard should represent an antibody activity (absorbance value) midway between the upper and central points and the weak positive standard should represent an antibody activity midway between the central and lower points of the linear portion of the curve. Owing to inherent differences among assay systems, antibody activities should be expressed in relative rather than in absolute terms. It is recommended that the antibody activity of the strong positive standard should denote 100% positivity. The activities of the weak positive and negative standards should then be expressed as relative percentages. Every set of international reference standards should be accompanied by an information sheet which includes, among other things, a plot of the dose/response curve and an indication of the dilutions used to prepare the standards.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Brucella abortus/inmunología , Brucelosis Bovina/diagnóstico , Ensayo de Inmunoadsorción Enzimática/veterinaria , Cooperación Internacional , Animales , Brucelosis Bovina/sangre , Brucelosis Bovina/inmunología , Bovinos , Relación Dosis-Respuesta Inmunológica , Ensayo de Inmunoadsorción Enzimática/normas , Lipopolisacáridos/inmunología , Juego de Reactivos para Diagnóstico/veterinaria , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
Enzyme-linked immunosorbent assay (ELISA) techniques for the detection of antibodies are now widely used throughout the world for the diagnosis of infectious diseases in veterinary medicine. Although many laboratories have independently developed ELISA techniques for their own purposes, little progress has been made with respect to the international standardisation and validation of these techniques. This lack of international conformity is of major concern to organisations such as the Office International des Epizooties (OIE), the United Nations Food and Agriculture Organisation (FAO), the World Health Organisation (WHO) and the International Atomic Energy Agency (IAEA) which are involved in the establishment of international guidelines and programmes for the control, surveillance and/or eradication of infectious diseases. In this regard, a Joint FAO/IAEA Meeting of Consultants was convened in Vienna in January 1992 to review aspects of ELISA data expression, primary reference standards, quality assurance and diagnostic validation. Based on the consensus derived from this meeting, the authors describe procedures which are recommended as a platform on which to build definitive guidelines for international standardisation of ELISA protocols and reagents, in cooperation with the OIE and the OIE Reference Laboratories.
Asunto(s)
Anticuerpos/análisis , Enfermedades Transmisibles/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Animales , Unión Competitiva , Enfermedades Transmisibles/diagnóstico , Ensayo de Inmunoadsorción Enzimática/normas , Control de Calidad , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
The performance of 2 competitive enzyme-linked immunosorbent assays (C-ELISA) was compared with the reference C-ELISA I for the detection of antibodies to bluetongue virus (BTV). One of the assays (C-ELISA II) used a group-specific monoclonal antibody (MAb) to BTV, obtained from the American Type Culture Collection (8A3B-6) and tissue culture (TC)-derived BTV antigen (Ag), and the other assay (C-ELISA III) used BTV core protein VP7 (expressed in yeast) and the reference MAb (Pirbright Laboratory, 3-17-A3). Test sera were obtained by sequential blood samples from 22 calves, each inoculated with a different serotype (T) of BTV (South African [SA] T-1-T-16 and T-18-T-20 and USA T-11, T-13, and T-17). Sera were also obtained from 4 calves and 4 sheep inoculated with USA BTV T-10 and from several groups of calves exposed to single or multiple doses of epizootic hemorrhagic disease virus (EHDV) T-1-T-4 grown in TC (BHK-21) or suckling mouse brain (SMB). A total of 618 bovine and ovine field sera collected from BT-free and BT-endemic areas were also tested. The C-ELISA III was more sensitive than the C-ELISA II in the detection of anti-BTV antibody in sera from cattle and sheep early after infection with BTV. Seroconversion was demonstrated by the 3 C-ELISAs in all animals inoculated with BTV by 20 days postinfection (DPI), except in calves that received SA T-3 or USA T-13, which became positive at 40 DPI.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anticuerpos Antivirales/sangre , Virus de la Lengua Azul/inmunología , Lengua Azul/diagnóstico , Enfermedades de los Bovinos/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Animales , Anticuerpos Monoclonales , Especificidad de Anticuerpos , Antígenos Virales/inmunología , Unión Competitiva , Bovinos , Estudios de Evaluación como Asunto , Inmunodifusión , Sensibilidad y Especificidad , Ovinos , Proteínas del Núcleo Viral/inmunologíaRESUMEN
Two groups of 10 pregnant cows were inoculated with bluetongue virus type 11 at either 40 or 60 days of gestation. All the cows became infected as judged by the detection of viraemia and seroconversion but they showed no clinical signs. Seventeen of the cows produced live calves none of which showed any evidence of prenatal infection. After challenge with the same virus all the calves became viraemic and seroconverted. The response to challenge of the two groups did not differ from that of a control group challenged at the same time. It was concluded that the infection of pregnant cows in early gestation with this virus did not result in the transplacental infection of the fetuses and did not produce immunotolerant, latently infected calves.
Asunto(s)
Animales Recién Nacidos/microbiología , Lengua Azul/congénito , Enfermedades de los Bovinos/congénito , Complicaciones Infecciosas del Embarazo/veterinaria , Resultado del Embarazo/veterinaria , Animales , Lengua Azul/microbiología , Lengua Azul/transmisión , Virus de la Lengua Azul/aislamiento & purificación , Bovinos , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/transmisión , Femenino , Embarazo , Complicaciones Infecciosas del Embarazo/microbiologíaRESUMEN
Analyses of reassortant and parental strains of BTV serotypes 3 and 10, in serum neutralization tests, confirmed the major role of outer capsid protein VP2 in determination of virus serotype and its involvement in serum neutralization. However, a reassortant BTV strain (R70), containing protein VP5 derived from BTV 3 and VP2 derived from BTV 10, cross-neutralized with both parental virus strains (BTV 3 and BTV 10). It is concluded that VP5 also plays some part in serotype determination of these virus isolates, as analyzed by serum-neutralization, but its role may be less significant than that of VP2.
Asunto(s)
Virus de la Lengua Azul/inmunología , Cápside/inmunología , Reoviridae/inmunología , Animales , Northern Blotting , Virus de la Lengua Azul/clasificación , Virus de la Lengua Azul/genética , Proteínas de la Cápside , Línea Celular , Reacciones Cruzadas , Electroforesis en Gel de Poliacrilamida , Pruebas de Neutralización , Hibridación de Ácido Nucleico , ARN Bicatenario/genética , ARN Viral/genética , SerotipificaciónRESUMEN
Bluetongue (BT) virus-specific ovine T-cell lines were prepared from BT virus-infected sheep by three cycles of alternate stimulation and resting culture in vitro. In antigen-specific proliferation assays and/or cytotoxicity assays, most of these T-cell lines responded not only to homologous serotype virus but also heterologous serotype viruses. This cross-reactivity did not correlate with the relatedness of serotypes as defined by cross-neutralizing antibodies. One cell line, 58-014, has grown continuously for more than 7 months without loss of antigen specificity. However, most of the cell lines lost their antigen specificity 2-4 months after cultivation. Certain BT virus-specific T-cell lines were able to reduce BT virus replication in autologous skin fibroblast cell culture.
Asunto(s)
Virus de la Lengua Azul/inmunología , Reoviridae/inmunología , Linfocitos T/inmunología , Animales , Virus de la Lengua Azul/clasificación , Línea Celular , Reacciones Cruzadas , Epítopos/inmunología , Activación de Linfocitos , Serotipificación , Ovinos , Linfocitos T Citotóxicos/inmunologíaRESUMEN
In the light of the recent outbreaks of rinderpest in Africa a further assessment of the efficacy of the simultaneous inoculation of rinderpest virus vaccine and contagious bovine pleuropneumonia vaccine was undertaken. Groups of cattle were inoculated with a dual preparation of rinderpest vaccine virus and Mycoplasma mycoides subspecies mycoides or M mycoides alone. These groups were then challenged with M mycoides, first unsuccessfully by an in-contact challenge method and then by subcutaneous challenge. All animals were examined clinically after challenge for evidence of contagious bovine pleuropneumonia and serologically for rinderpest virus and M mycoides mycoides antibodies. There was no evidence that the serological response to the dual vaccine was in any way less than that to either agent given alone and no clinical disease was detected in these animals after in-contact challenge. However, after subcutaneous challenge, the dual vaccinated groups reacted similarly to an unvaccinated control group and unlike the group vaccinated only with M mycoides. This would indicate that the rinderpest virus component of the dual vaccine interfered with the ability of the M mycoides component to induce a fully effective immune response. In the pan African rinderpest campaign the use of the dual vaccine in areas where contagious bovine pleuropneumonia occurs should be carefully considered; in areas where the disease does not occur it is contraindicated.
Asunto(s)
Vacunas Bacterianas/inmunología , Mycoplasma mycoides/inmunología , Virus de la Peste Bovina/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antivirales/biosíntesis , Bovinos , Enfermedades de los Bovinos/prevención & control , Pruebas de Fijación del Complemento , Combinación de Medicamentos , Ensayo de Inmunoadsorción Enzimática , Masculino , Pruebas de Neutralización , Pleuroneumonía Contagiosa/prevención & control , Peste Bovina/prevención & control , Vacunación/veterinaria , Vacunas AtenuadasRESUMEN
A South African isolate of bluetongue virus type 3 was inoculated intradermally into three different breeds of British sheep under conditions designed to test its virulence in animals under stress. All animals inoculated developed a pyrexia and viraemia followed by clinical evidence of bluetongue disease. Marked alterations in serum enzyme levels, in particular of creatine phosphokinase, lactate dehydrogenase and aldolase occurred in the more severely affected animals. Nine out of the 12 inoculated animals subsequently died. No major differences in response could be detected in the different breeds of sheep nor in the stressed compared with the unstressed groups. The virulence of this bluetongue virus isolate was thereby confirmed and its potential risk to the British sheep industry. Consequently, stringent import regulations must be maintained to prevent its entry into Britain.
Asunto(s)
Virus de la Lengua Azul/patogenicidad , Lengua Azul/microbiología , Reoviridae/patogenicidad , Animales , Anticuerpos Antivirales/biosíntesis , Coagulación Sanguínea , Lengua Azul/sangre , Lengua Azul/inmunología , Virus de la Lengua Azul/inmunología , Creatina Quinasa/sangre , Ensayo de Inmunoadsorción Enzimática , Fructosa-Bifosfato Aldolasa/sangre , Inmunodifusión , L-Lactato Deshidrogenasa/sangre , Masculino , Pruebas de Neutralización , Ovinos , Estrés Fisiológico/veterinaria , Viremia/veterinaria , VirulenciaRESUMEN
Groups of sheep inoculated with bluetongue virus type 4 were challenged at various intervals after inoculation (from seven to 70 days) with bluetongue virus type 3. Examination of the clinical and serological response showed that animals were protected from challenge with a second bluetongue virus for up to 14 days after the inoculation of the first virus type. An adoptive transfer experiment in monozygotic sheep involving both antibody and T lymphocytes was carried out. Only partial protection was observed against heterologous virus challenge, indicating that although the T cell response has a cross-protective component, antibody is not involved. These observations indicate that current vaccination procedures should be reappraised, particularly in terms of revaccination with multiple bluetongue virus type.
Asunto(s)
Anticuerpos Antivirales/inmunología , Virus de la Lengua Azul/inmunología , Lengua Azul/inmunología , Reoviridae/inmunología , Animales , Virus de la Lengua Azul/clasificación , Ovinos/inmunologíaRESUMEN
Immunological studies with bluetongue virus have indicated that protection from re-infection involves components of both the humoral and cellular immune response. However, it was found that the humoral response was type-specific, whilst the cellular immune response, particularly through the action of cross-reactive cytotoxic T lymphocytes, gave rise to heterotypic protection. Work involving simultaneous and sequential inoculation of live virus and the inoculation of various inactivated preparations has further characterized the type of vaccine formulation needed for efficient protection in multitype endemic areas. The authors cite these studies on bluetongue virus as an example of an immunological approach to vaccine design that is too often ignored by vaccine manufacturers and yet clearly yields results.