Gumboro disease in poultry; cause. symptom, and prevention

03/02/2023

30/09/2022

Control and Treatment of Infectious Bursal Disease
There is no treatment. Rigorous disinfection of contaminated farms after depopulation has achieved limited success. Live vaccines of chicken embryo or cell-culture origin and of varying low pathogenicity can be administered by eye drop, drinking water, or SC routes at 1–21 days of age. Replication of these vaccines and thus the immune response can be altered by maternal antibody, although the more virulent vaccine strains can override higher levels of maternal antibody. Vectored vaccines that express the IBDV VP2 protein in herpesvirus of turkeys (HVT) can be used in ovo or at hatch. These HVT-IBD vaccines are not affected by maternal antibodies. Vaccines that use live-attenuated viruses bound to antibodies (immune-complex vaccines) are also available for in ovo or at hatch administration.
High levels of maternal antibody during early brooding of chicks in broiler flocks (and in some commercial layer operations) can minimize early infection, subsequent immunosuppression, or both. Breeder flocks should be vaccinated one or more times during the growing period, first with a live vaccine and again just before egg production with an oil-adjuvanted, inactivated vaccine. Inactivated vaccines of chicken embryo, bursa, or cell-culture origin are available. The latter vaccines induce higher, more uniform, and more persistent levels of antibody than do live vaccines. The immune status of breeder flocks should be monitored periodically with a quantitative serologic test such as virus neutralization or ELISA. If antibody levels decrease, hens should be revaccinated to maintain adequate immunity in the progeny.
The goal of any vaccination program for IBD should be to use vaccines that most closely match the antigenic profile of the field viruses. Diagnostic testing for the genomic sequences of field strains can be used to select the most appropriate vaccination program.

30/09/2022

Diagnosis of Infectious Bursal Disease
Diagnosis can be accomplished by clinical evaluation of the cloacal bursa for macroscopic and microscopic lesions followed by molecular detection of the viral VP2 gene using RT-PCR
Sequence analysis of the VP2 gene is used to identify the IBDV genotype
Virus isolation in chicken embryos or chicken embryo fibroblast cell cultures is possible but often not necessary
Initial diagnosis of infectious bursal disease is accomplished by the observation of gross lesions in the cloacal bursa. This is followed by microscopic analysis of the bursa for lymphocyte depletion in the follicles. Molecular diagnostic assays are most often used to identify IBDV in diagnostic samples. The reverse-transcriptase-PCR assay is used to identify the viral genome in bursa tissue. Sequence alignments and phylogenetic analysis of the VP2 coding region has been used to further characterize the viruses into genogroups. Samples for molecular diagnostic testing are typically collected after maternal antibodies have waned.
IBDV may be isolated in 8- to 11-day-old, antibody-free chicken embryos with inocula from birds in the early stages of disease. The chorioallantoic membrane is more sensitive to inoculation than is the allantoic sac. Some strains of IBDV may also be isolated in cell cultures that include chicken embryo fibroblasts, cells from the cloacal bursa, and established avian and mammalian cell lines. Cell culture–adapted strains of IBDV produce a cytopathic effect and may be used for quantitative titration of the virus and virus-neutralization assays.
Serology can be used to detect the presence of antibodies to IBDV in convalescent chicks. Commercially available ELISA kits are most often used to quantitate IBDV antibodies. The presence of IBDV antibodies in chicks is not always an indication of infection because most young chicks have maternal antibodies.

30/09/2022

Etiology and Transmission of Infectious Bursal Disease
Infectious bursal disease is caused by a birnavirus (infectious bursal disease virus; IBDV) that is most readily isolated from the bursa of Fabricius but may be isolated from other organs. It is shed in the f***s and transferred from house to house by fomites. It is very stable and difficult to eradicate from premises.
Two serotypes of IBDV have been identified. The serotype 1 viruses cause disease in chickens and, within them, antigenic variation can exist between strains. Antigenic drift is largely responsible for this antigenic variation, but antigenic differences can also occur through genome homologous recombination. Serotype 2 strains of the virus infect chickens and turkeys but have not caused clinical disease or immunosuppression in these hosts. IBDVs have been identified in other avian species, including penguins, and antibodies to IBDV have been seen in several wild avian species. The contribution of IBDV to disease in these wild birds is unknown.

30/09/2022

Infectious bursal disease (IBD) is seen in young domestic chickens worldwide and is caused by infectious bursal disease virus (IBDV). Symptoms of the clinical disease can include depression, watery diarrhea, ruffled feathers, and dehydration. Depending on the IBDV strain and presence of maternal immunity, the disease can also present as a clinical or subclinical disease in young chicks. For both clinical and subclinical forms of the disease, all pathogenic IBDVs cause lesions in the bursa of Fabricious. The cloacal bursa can become enlarged, with a yellowish colored transudate on the surface. Hemorrhages on the serosal and mucosal services are sometimes observed. Atrophy of the bursa, which includes the loss of B-lymphocytes, occurs approximately 7-10 days after infection. Immunosuppression is directly related to this loss of B-lymphocytes, but immunosuppression and related secondary infections are typically seen in birds that recover from the disease. Severity of the immunosuppression depends on the virulence of the infecting virus and age of the host.

29/09/2022

Prevention
Vaccination, including passive protection via breeders, vaccination of progeny depending on virulence and age of challenge. In most countries breeders are immunised with a live vaccine at 6-8 weeks of age and then re-vaccinated with an oil-based inactivated vaccine at 18 weeks. A strong immunity follows field challenge. Immunity after a live vaccine can be poor if maternal antibody was still high at the time of vaccination.
When outbreaks do occur, biosecurity measures may be helpful in limiting the spread between sites, and tracing of contacts may indicate sites on which a more rebust vaccination programme is indicated.This shows the anatomical relationship between the bursa, the re**um and the vent. This bursa is from an acutely affected broiler. It is en­larged, turgid and oedematous.

29/09/2022

Signs
Depression.
Inappetance.
Unsteady gait.
Huddling under equipment.
Vent pecking.
Diarrhoea with urates in mucus.
Post-mortem lesions
Oedematous bursa (may be slightly enlarged, normal size or reduced in size depending on the stage), may have haemorrhages, rapidly proceeds to atrophy.
Haemorrhages in skeletal muscle (especially on thighs).
Dehydration.
Swollen kidneys with urates.
Diagnosis
Clinical disease - History, lesions, histopathology.
Subclinical disease - A history of chicks with very low levels of maternal antibody (Fewer than 80% positive in the immunodifusion test at day old, Elisa vaccination date prediction < 7 days), subsequent diagnosis of 'immunosuppression diseases' (especially inclusion body hepatitis and gangrenous dermatitis) is highly suggestive. This may be confirmed by demonstrating severe atrophy of the bursa, especially if present prior to 20 days of age.
The normal weight of the bursa in broilers is about 0.3% of bodyweight, weights below 0.1% are highly suggestive. Other possible causes of early immunosuppression are severe mycotoxicosis and managment problems leading to severe stress.
Variants: There have been serious problems with early Gumboro disease in chicks with maternal immunity, especially in the Delmarva Peninsula in the USA. IBD viruses have been isolated and shown to have significant but not complete cross-protection. They are all sero-type 1. Serology: antibodies can be detected as early as 4-7 days after infection and these last for life. Tests used are mainly Elisa, (previously SN and DID). Half-life of maternally derived antibodies is 3.5- 4 days. Vaccination date prediction uses sera taken at day old and a mathematical formula to estimate the age when a target titre appropriate to vaccination will occur.

Differentiate clinical disease from: Infectious bronchitis (renal); Cryptosporidiosis of the bursa (rare); Coccidiosis; Haemorrhagic syndrome.

29/09/2022

A viral disease, seen worldwide, which targets the bursal component of the immune system of chickens. In addition to the direct economic effects of the clinical disease, the damage caused to the immune system interacts with other pathogens to cause significant effects. The age up to which infection can cause serious immunosuppression varies between 14 and 28 days according to the antigen in question. Generally speaking the earlier the damage occurs the more severe the effects.
The infective agent is a Birnavirus (Birnaviridae), Sero-type 1 only, first identified in the USA in 1962. (Turkeys and ducks show infection only, especially with sero-type 2).
Morbidity is high with a mortality usually 0- 20% but sometimes up to 60%. Signs are most pronounced in birds of 4-6 weeks and White Leghorns are more susceptible than broilers and brown-egg layers.
The route of infection is usually oral, but may be via the conjunctiva or respiratory tract, with an incubation period of 2-3 days. The disease is highly contagious. Mealworms and litter mites may harbour the virus for 8 weeks, and affected birds excrete large amounts of virus for about 2 weeks post infection. There is no vertical transmission.
The virus is very resistant, persisting for months in houses, faeces etc. Subclinical infection in young chicks results in: deficient immunological response to Newcastle disease, Marek's disease and Infectious Bronchitis; susceptibility to Inclusion Body Hepatitis and gangrenous dermatitis and increased susceptibility to CRD.

29/09/2022

Control and Prevention of Gumboro Disease
If Gumboro is an issue, vaccination is the most effective control method, either through enhanced MDA in parent stock or through active immunity by means of direct vaccination of chicks. Vaccination policy against Gumboro disease tends to vary by area and the degree of challenge – in cases where the level of challenge is low, birds can develop immunity and vaccination will not be required. However, where vaccination is used, all protocols strive to provide passive protection to the hatching chick, followed by active immunization and a series of boosts in layer and breeder flocks (Saif, 1998).
Broilers drinking
Live vaccines are usually administered in drinking water when the birds are 12 – 21 days old.
If there is a challenge to birds from Gumboro, live vaccines are normally administered through drinking water or eye-drops to chicks at 12-21 days. Saif (1998) refers to unpublished data that casts some doubt on this controversial practice. A live vaccine at 4-10 weeks, followed by an inactivated oil-adjuvanted vaccine at approximately 16 weeks, may be used on parent birds in order to achieve high levels of MDA. Repeated vaccination of chicks is practised in some flocks to counteract declining levels of MDA. It is important that vaccination of chicks is given when MDA levels are low so as to avoid MDA neutralizing the effect of the vaccine.
Removal of the virus from contaminated sites can be difficult, as large quantities are excreted and the virus is stable. An all-in all-out housing policy, coupled with stringent disinfection with formaldehyde and iodophors, can prove effective in reducing challenge to levels and enhancing the impact of vaccination.
Spread of the disease has been associated with the use of infected manure on fields adjoining poultry housing. It is therefore advisable to locate poultry manure away from poultry houses and to store for more than 3 months. Protecting manure heaps from wildlife could also be desirable in controlling infection. Outbreaks of recent virulent epidemics of IBD have been spread rapidly by litter taken from infected houses. There are MAFF and Department guidelines concerning manure handling.
Routine blood testing can be conducted to assess the immune status of flocks.

13/11/2021

Clinical Findings of Infectious Bursal Disease
Infectious bursal disease is highly contagious; results of infection depend on age and breed of chicken and virulence of the virus. Infections may be subclinical or clinical. Infections before 3 weeks of age are usually subclinical. Chickens are most susceptible to clinical disease at 3–6 weeks of age when immature B cells populate the bursa and maternal immunity has waned, but severe infections have occurred in Leghorn chickens up to 18 weeks of age.
Early subclinical infections are the most important form of the disease because of economic losses. They cause severe, long-lasting immunosuppression due to destruction of immature lymphocytes in the bursa of Fabricius, thymus, and spleen. The humoral (B cell) immune response is most severely affected; the cell-mediated (T cell) immune response is affected to a lesser extent. Chickens immunosuppressed by early IBDV infections do not respond well to vaccination and are predisposed to infections with normally nonpathogenic viruses and bacteria. Common diseases are usually exacerbated by IBDV infections. Some strains of IBDV can cause subclinical infections in older birds (3–6 weeks old), which leads to losses from poor feed efficiency and longer times to market. In these cases, the immunosuppression is usually transient, and convalescent birds may recover most or all of their humoral immune function. However, secondary infections that occur during the transient immunosuppression can cause significant economic losses.
In clinical infections, onset of the disease occurs after an incubation of 3–4 days. Chickens may exhibit severe prostration, incoordination, watery diarrhea, soiled vent feathers, vent picking, and inflammation of the cloaca. Flock morbidity is typically 100%, and mortality can range from 5% to greater than 60% depending on the strain of virus and breed of chicken. Mortality is typically higher in layer breeds compared with broiler chickens. Recovery occurs in 20%) were first detected in Europe. They spread throughout the Middle East, Asia, and Africa, were detected in South and Central America in 1999, and in the USA in 2009

13/11/2021

GUMBORO DISEASE in Chickens , Infectious Bursal Disease Symptoms, IBD, Poultry Diseases
Key Points
Infectious bursal disease, caused by infectious bursal disease virus, is a disease of young chickens. The virus infects immature B-lymphocytes and causes an immune suppression that leads to secondary infections in convalescent birds.
The virus is found worldwide, and diagnosis is through clinical evaluation of the cloacal bursa and molecular identification of the viral genome.
Control of IBD is accomplished using vaccination of breeder flocks to induce maternal immunity in young chicks. Antigenic drift requires the use of vaccines that closely match the antigenic structure of the infecting virus. Vaccination in ovo or young chicks using vectored or live-attenuated vaccines can help boost protection as maternal antibodies wane.

23/07/2021

Gumboro Disease or Infectious bursal disease virus (IBDV) is a chicken disease targeting the Bursa of Fabricius, an important organ in the young chicken's developing immune system. The causative agent, a Birna virus, destroys immature B-lymphocytes in the Bursa of Fabricius resulting in immunosuppression. Very virulent strains of IBDV can result in mortality of up to 40%. Control is best achieved by improved biosecurity and vaccination.

23/07/2021

Prevention
Biosecurity should be a primary focus when it comes to prevention and control of IBD. However, experience with the IBD virus has shown that biosecurity alone is not an effective control. Commercial broiler breeder flocks are vaccinated to produce maternal immunity that is passed on to the chick for IBD control. Unfortunately, many people with backyard flocks do not vaccinate their birds for the IBD virus. Movement of backyard birds to exhibits, fairs, shows, etc., increases the risk of an outbreak.
New birds brought on the property or birds returning home after a fair or show should be quarantined from the rest of your birds for 30 days. If the quarantined birds have been exposed to something, they will start to show symptoms within 30 days. If they do show symptoms, at least you have not infected your entire flock and only the birds that left the farm are at risk. During those 30 days, do not wear the same boots or use the same equipment around your original flock as around your quarantined birds. You don’t want to track whatever the quarantined birds may have been exposed to over to the rest of your flock.
Treatment
Unfortunately, there is no known treatment for the IBD virus.
Public Health
Infectious bursal disease virus does not appear to be zoonotic. There is no evidence that IBD virus can infect people or other animals.
Sources of Help
Here are some sources of help if you are concerned about infectious bursal disease in your backyard flock or need assistance with disease diagnosis:

23/07/2021

Role of Bursa of Fabricius
The bursa of Fabricius plays an important part in the disease. The bursa is the “assembly plant” for the immune system. The bursa produces B cells which, in turn, produce antibodies to help the immune system fight off disease challenges. The B-cell system develops during embryogenesis (formation and development of an embryo after fertilization) and the first few weeks after hatch.

Between embryonic day 8 and 15, pre-bursal B-cell precursors migrate from the embryonic spleen and bone marrow into the bursa (Kaspers, 2014), where they receive signals from the bursa that trigger the maturation process to begin and allow these B cells to be programmed to become mature antibody-producing B lymphocytes. Once fully mature, the B-lymphocyte cells leave the bursa and populate secondary lymphatic tissues, where they may come in contact with pathogens or perhaps antigens delivered through vaccination.

If the bursa is damaged by IBD, it can no longer assemble enough lymphocytes to protect the bird from disease challenges. The disease targets the lymphocytes in the bursa of Fabricius, compromising the immune system, resulting in immunosuppression and susceptibility to other secondary infections. The bursa of chicks infected with IBD may triple in size as the disease progresses but will then shrink as the disease runs its course. Unfortunately, during the disease, the bursal tissues are often damaged or destroyed, leaving surviving chickens with reduced immune system capabilities. Especially for backyard or commercial birds raised without antibiotics, once the birds become immune-suppressed, other opportunistic pathogens begin to overwhelm the weakened immune system, and this can lead to a variety of secondary infections such as E. coli, airsacculitis, Clostridium, and Mycoplasma. In most cases, if the bird can remain IBD free until 3 weeks of age, enough lymphocytes can be instructed to become antibody-producing cells to minimize the immunosuppressive effects of an IBD challenge.

23/07/2021

Infectious bursal disease (IBD, Gumboro)


IBD, INFECTIOUS BURSAL DISEASE



AETIOLOGY:
Double stranded RNA virus, it belongs to the genus Avibirnavirus of the family Birnaviridae, very resistant in the environment. Two Serotypes can be identified; the strains that causes the disease in poultry belongs to Serotype 1, while the strains of Serotype 2 are apathogenic.



TRANSMISSION:
Direct: by faeces.

Indirect: by fomites, farm staff and insects such as Alphitobius diaperinus.

CLINICAL SIGNS:
Diarrhoea, bristled feathers, septic shock, depression, prostration and comb paleness. Secondary processes appear due to immunosuppression: less response to vaccines, more incidence of coccidiosis and other pathological processes. It is possible to make a presumptive diagnosis based on the appearance of symptoms such as weakness, white diarrhoeas, bristled feathers, and lesions such as muscular haemorrhages, oedema and haemorrhages or bursal atrophy.



LESIONS:
Increased bursal size, oedema with gelatinous and haemorrhagic content, which over the course of the time becomes atrophic. Haemorrhages in thighs and breast muscles. Renal alterations: inflammation and accumulation of urate. It is possible to estimate the degree of virulence of the virus and its lymphocytary depletion capacity by doing a histological analysis of the bursal tissue.



DIAGNOSIS:
Causal agent identification: Isolation, RT-PCR, RFLP.

Serological: ELISA.

TREATMENT, PREVENTION AND CONTROL:
There is no effective treatment against the disease, although birds may be helped with drugs to treat symptoms so as to control secondary agents and the effects of immunosuppression.

One of the basics of prevention is the use of vaccination with inactivated vaccines in breeders so as to supply good passive immunity to the progeny. Chicks should be vaccinated with live vaccines when the level of maternal immunity is adequate so that the vaccine is not neutralised.

Moreover, and no less important, it is fundamental to ensure good levels of biosecurity, disinfections, and pest control as well as avoiding multi-age systems for reducing the incidence of the disease

18/07/2021

A hen can lay only one egg in a day and will have some days when it does not lay an egg at all. The reasons for this laying schedule relate to the hen reproductive system. A hen’s body begins forming an egg shortly after the previous egg is laid, and it takes 26 hours for an egg to form fully. So a hen will lay later and later each day. Because a hen’s reproductive system is sensitive to light exposure, eventually the hen will lay too late in a day for its body to begin forming a new egg. The hen will then skip a day or more before laying again. See the related article discussing the reproductive tract of a chicken for more information on the specifics of egg production.
Also, hens in a flock do not all begin to lay on exactly the same day, nor do they continue laying for the same length of time. Figure 1 shows a typical egg production curve for a flock. The flock comes into production quickly, peaks, and then slowly reduces the level of production.

06/07/2021

Infectious bursal disease
Serotype 1 of IBDV belonging to the family Birnaviridae and commonly known as Gumboro disease virus is a significant cause of diarrhoea, immunosuppression and mortality in chickens. Virus transmission is via infected food and water, virus primarily replicating in the oropharynx resulting in viraemia and infection of the bursa. Non-pathogenic serotype 2 strains of IBDV from turkeys also occur and the determinant of pathogenicity appears to be the tropism for bursa of Fabricius [116]. A difficulty in controlling IBDV disease in the field is the emergence of variants against which existing vaccines are partially protective.

Control of IBDV is with egg and/or tissue culture attenuated live vaccines. They are given by spray or drinking water when residual MDA has declined sufficiently for the vaccine to take, and laying hens are boosted with killed oily vaccine by the SC or IM route. Serotype 2 IBDV strains cause sub clinical infection in chickens and turkeys. Efficacy of primary in ovo inoculation of an experimental live IBDV vaccine was reported recently [117]. The next generation of IBDV vaccines are likely to be multivalent bio-tech vaccines namely one vaccine for two or more poultry virus diseases.

06/07/2021

Adenoviruses
Adenoviruses (Ads) are associated with the common cold and cause respiratory, intestinal, and eye infections in humans. More than 100 Ad serotypes have been isolated and characterized from humans and from most mammalian and avian species (Ishibashi, 1984). Of the human Ads, types 2 and 5 have been most extensively studied as recombinant viral vectors (Lai et al., 2002; Babiuk and Tikoo, 2000). Since Ads are mucosally transmitted, they are attractive vectors for delivering vaccines to mucosal surfaces. Ads have well-defined molecular biology, can be grown to extremely high titers (1010 to 1011 pfu/mL), thus reducing the cost of vaccine production and delivery, and can infect a variety of cells and tissues. An important observation is that Ads can infect and be expressed in dendritic cells (DCs), the most potent antigen presenting cell (APC). Ads can also infect a variety of postmitotic cells. A number of effective Ad vaccines have been licensed for use in humans and animals, providing extensive experience with safety and efficacy. Indeed, millions of military recruits have been safely and effectively protected against acute respiratory disease following oral mucosal immunization with Ad4 and Ad7 vaccines in gelatin-coated capsules (Top et al., 1971a; Top et al., 1971b; Top, 1975).

Ads are nonenveloped viruses containing a linear double-stranded DNA genome that varies in size (30 to 45 kb), depending on the species from which they were isolated. Two main types of recombinant Ads have been developed: replication-competent and replication-defective. Replication-competent Ads are constructed by deleting the early 3 (E3) region genes, which modulate host immune responses to the virus but are not essential for replication. These vectors do not require complementing cells for growth in vitro and can be used at lower doses to induce immune responses in vivo. A disadvantage of replication-competent rAds is they can accept only 3 to 4 kb of foreign DNA. Replication-defective Ads lack the E1 region genes, which are essential for virus replication. Replication-defective Ads require a complementing cell line for growth in vitro. E1 and E1, E3–deleted Ads can accommodate up to 8.3 kb of foreign DNA inserted into either the E1 or E3 region. Replication-defective Ad vectors have been used to deliver vaccines in animal models and in the veterinary field (Babiuk and Tikoo, 2000). They have provided protection against challenge with rabies virus (Vos et al., 2001; Tims et al., 2000; Lees et al., 2002); bovine herpesvirus (Reddy et al., 2000; Gogev et al., 2002); infectious bursal disease virus (Sheppard et al., 1998); foot-and-mouth disease virus (Moraes et al., 2002); measles virus (Sharpe et al., 2002); Ebola virus (Sullivan et al., 2000); SHIV (Shiver et al., 2002); and HIV-1 (Yoshida et al., 2001).

Recently, helper-dependent “gutless” (or perhaps, more appropriately, “gutted”) Ads have been developed that lack all adenovirus structural genes (Kumar-Singh and Chamberlain, 1996; Kochanek et al., 1996; Fisher et al., 1996). These vectors contain only the inverted terminal repeats (ITRs) required for replication and the cis-acting Ad encapsidation signals necessary for packaging. The deletion of all the viral genes permits gutted Ad vectors even greater cloning capacity and addresses the problem of antivector immunity. However, these vectors are difficult to produce and require the use of a helper virus to provide all the viral proteins in trans. Since a helper virus is used to produce the gutted vector, one of the main problems associated with them is the final separation of helper and vector viruses during purification. However, recent improvements in the production of gutless Ad vectors has helped in the obtainment of purified vectors that contain 0.1% helper virus (Parks et al., 1996). Although gutted Ad vectors have been tested in gene therapy, they have yet to be tested in vaccine studies.

Human Ad5 is the most commonly used vector for preclinical studies. A hurdle in extrapolating studies of human rAd5-based vectors from animal models to humans is the presence of anti-Ad5 neutralizing antibodies in humans. Humoral immune responses to Ad5 are strong and are found in up to 45% of adults in the United States. Depending on route of delivery, they have been shown to decrease the infection efficacy in animal models as well as humans. Strategies to bypass preexisting immunity include switching of Ad serotype (Morral et al., 1999; Mastrangeli et al., 1996; Kass-Eisler et al., 1996) and the use of animal adenoviruses (Farina et al., 2001; Hofmann et al., 1999; Moffatt et al., 2000). While an advantage of animal adenoviruses is that neutralizing antibodies are absent, the lack of knowledge regarding their biology—including tropism in humans—and the possibility of in vivo recombination with human types has so far limited their application. Therefore, extensive screening was conducted to identify human adenoviruses with low seroprevalence and Ad type 35 (Vogels et al., 2003). Subsequently, replication-deficient human Ad35 vectors were constructed and were shown to bypass anti-Ad5 neutralizing antibodies and to have tropism similar to that of Ad5 (Vogels et al., 2003).

We were among the first groups to explore recombinant human Ads as mucosal vaccines and have been strong proponents of its application against HIV. rAds have been described for a variety of animal viruses, including hepatitis B virus, hepatitis C virus, vesicular stomatitis virus (VSV), herpes simplex virus, rabies virus, parainfluenza virus, and HIV.

Today, studies of rAd vectors are generating much interest as vaccines against HIV (Voltan and Robert-Guroff, 2003). Most groups have pursued replication-defective Ad5/HIV and SIV recombinants. These have been found to have good immunogenicity. Recently, a study demonstrating that immunization with rAd/SIVgag, with or without prior priming with SIVgag DNA, elicited potent cellular immune responses and protected macaques against SHIV89.6 challenge. This has led to a phase I trial being conducted in the United States, evaluating DNA versus rAd prime, followed by rAd boost, and a phase II rAd/HIVgag evaluation is being conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and Merck in a number of countries. Additionally, some groups have pursued use of replication-competent rAd vectors, using a strategy based on sequential immunization with rAd of different serotypes. Studies in nonhuman primates have shown induction of strong humoral, cellular, and mucosal immune responses.

Tuberculosis, caused by Mycobacterium tuberculosis, remains a global epidemic: one-third of the world's population is infected, and 8 million new cases and 2 to 2.5 million deaths occur annually (Wang and Xing, 2002; Dye et al., 1999). Recently, a recombinant replication-defective Ad-based vaccine expressing M. tuberculosis Ag85A (AdAg85A) was engineered and evaluated for its potential to serve as a respiratory mucosal tuberculosis vaccine in a murine model of pulmonary tuberculosis (Wang et al., submitted). A single nasal immunization with AdAg85A provided potent protection against airway M. tuberculosis challenge. Indeed, mice immunized mucosally with AdAg85A were much better protected than those immunized parenterally with AdAg85A or even with bacillus Calmette-Guerin (BCG) vaccine. Such superior protection following nasal AdAg85A was mediated by both CD4-positive (CD4+) and CD8+ T cells and was correlated with greater accumulation and retention of antigen-specific T cells in the lung. Thus, these results lend further support to the critical advantage of respiratory mucosal vaccination over other routes of vaccination in the fight against tuberculosis