Studies of Adenoviruses (APC) in Volunteers

Bell, Joseph A.; Ward, Thomas G.; Huebner, Robert J.; Rowe, Wallace P.; Suskind, R. G.; Paffenbarger, Ralph S.

doi:10.2105/ajph.46.9.1130

Cited by 76 publications

(32 citation statements)

References 14 publications

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“…The short (1-to 2-day) incubation period is also characteristic of other experimental enteroviral infections [ECHO 28 (21) and "rhinoviruses" (22)] and is similar to influenza (23). In contrast, incubation periods for respiratory syncytial virus (9), parainfluenza viruses (24)(25)(26), and adenoviruses (27,28) Very few enteroviruses have been etiologically associated with acute respiratory disease. In this context, the differential patterns of pharyngeal and fecal excretion of such agents is of some interest.…”

Section: Discussionmentioning

confidence: 99%

Acute Respiratory Disease in Normal Volunteers Associated With Coxsackie a-21 Viral Infection. Iii. Response to Nasopharyngeal and Enteric Inoculation

Spickard¹,

Evans²,

Knight³

et al. 1963

J. Clin. Invest.

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Parsons. Bynoe, Pereira, and Tyrrell (8) conducted a volunteer study using Coxsackie A-2 1 virus and showed that this agent could produce a mild upper respiratory illness in young adults after an incubation period of 2 to 4 days. Virus was detected in pharyngeal specimens over a 6-day period of observation, but was less often found in fecal specimens. In two recent reports (5, 6), Coxsackie A-21 virus was associated with mild upper respiratory illness in military personnel at Camp Lejeune, North Carolina. Virus was readily recovered from pharyngeal specimens of ill recruits, and significant rises in neutralizing and hemagglutination-inhibiting antibodies were demonstrated.The evidence that this agent was a cause of human disease suggested the need for additional knowledge of its effects in man. Accordingly, studies were made in normal volunteers in which virus was administered by the nasopharyngeal route, or directly into the intestinal tract in subjects with no, intermediate, or high titers of homologous antibody. The study revealed that nasopharyngeal inoculation of subjects without measurable prechallenge antibody was followed by a systemic illness with fever and myalgia that was more severe when the inoculum was large. The presence of intermediate amounts of antibody before inoculation was associated with a syndrome of common cold, whereas men with high titers exhibited no illness. It was also found that the agent, although designated an enterovirus, was isolated most frequently from throat swabs. This finding was confirmed when it was found that direct intestinal inoculation produced only transient infection and no illness or antibody response. These findings are described in the following report. METHODS1 %olhteers. The men who participated in these experiments were volunteers from several federal correctional institutions. Selection was based on willingness to participate, good health, and on the presence of a suitable level of antibody to Coxsackie A-21 for a particular experiment.Clinical studies. Men were confined 3 per room for 3 to 4 days before and 3 weeks after viral inoculation. Examinations of the volunteers were made twice daily by two physicians who were unaware of the virus to be given, or of the antibody status of individual volunteers. Diagnosis of illness was made in a volunteer only by mutual agreement of both examiners. Oral temperatures were taken four times a day, and significant fever was considered to be any temperature greater than 37.50 C (99.50 F). Initial preinoculation leukocyte counts, sedimentation rate, and hemoglobin determination were obtained and then repeated on days 1, 2, 3, 5 to 9, and 12 to 15 after inoculation. A urine analysis was performed before and once after inoculation. Studies of liver function including bilirubin, alkaline phosphatase, transaminase, Bromsulphalein retention, thymol turbidity, and cephalin flocculation were made before and 3 days after inoculation. Electrocardiograms and chest roentgeno-840

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Section: Discussionmentioning

confidence: 99%

Acute Respiratory Disease in Normal Volunteers Associated With Coxsackie a-21 Viral Infection. Iii. Response to Nasopharyngeal and Enteric Inoculation

Spickard¹,

Evans²,

Knight³

et al. 1963

J. Clin. Invest.

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“…5 In the early to mid-1950s, a series of studies was conducted aimed at determining what type of illness(es) Ads could induce in humans (Bell et al 6 and references therein). These studies showed that experimentally infected volunteers infrequently exhibited minor respiratory illness following intranasal administration of Ad types 1, 2, 3, 5, and 6.…”

Section: Natural History Of Ad Infectionmentioning

confidence: 99%

“…6 Importantly, one of these studies, conducted at the Federal Industrial Reformatory at Chillicothe, Ohio, found that no respiratory disease outbreaks occurred among the reformatory population either immediately before, during, or after the experimental infections, suggesting that virus was not transmitted to noninoculated persons by casual contact with experimentally infected individuals. 6 Another study with Ad1 confirmed that intranasal inoculation of this serotype in humans lacking pre-existing neutralizing antibodies caused acute pharyngitis characterized by nasal exudates, sore throat, headache, and cervical adenitis. 7 Further experimental infections in which the eye was infected by conjunctival swabbing resulted in an illness similar to pharyngoconjunctival fever that was attributable to the inoculated Ad types 1, 3, 4, and 5.…”

Section: Natural History Of Ad Infectionmentioning

confidence: 99%

“…7 Further experimental infections in which the eye was infected by conjunctival swabbing resulted in an illness similar to pharyngoconjunctival fever that was attributable to the inoculated Ad types 1, 3, 4, and 5. 6,8 Pharyngoconjunctival fever is characterized by any combination of fever, pharyngitis, and conjunctivitis.…”

Section: Natural History Of Ad Infectionmentioning

confidence: 99%

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Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

Lichtenstein

Wold

2004

Cancer Gene Ther

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Replication-competent (RC) adenoviruses (Ads) are increasingly being developed as oncolytic vectors and as vehicles for delivering vaccine antigens. Although the safety of such vectors in humans is of paramount importance, these vectors pose additional special concerns. Specifically, the prospect of causing Ad-mediated disease in the patient, the amount and sites of Ad replication, the possibility of virus shedding leading to unintended transmission to patient contacts, and the potential for persistence in the inoculated individual must be evaluated. Previous experience with administration of wild-type and RC recombinant Ads to humans may shed light on some of these issues. Experimental infections of humans with natural Ad isolates and RC recombinant vectors show that in adults Ads cause mild or no disease, particularly with Ad serotypes 2 and 5, the serotypes most often used to make recombinant constructs. Other studies show that Ad can replicate in experimentally infected persons, that in some situations Ads can be shed and transmitted to close contacts, and that there is evidence for persistent/latent Ad infection in naturally infected individuals. Overall, these studies indicate that Ads can be safely administered to humans for the treatment of cancer and as antigen delivery vehicles suggesting that the continued development of RC oncolytic and vaccine vectors should be pursued.

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“…This suggests that by exploiting the properties that lead to a cancerous state, some viruses can preferentially kill tumor cells. Deliberate infection of individuals with wild-type viruses, however, raises significant safety concerns (Ward et al, 1955;Bell et al, 1956;Mitsui et al, 1957;Huneycutt et al, 1993;Stojdl et al, 2000). Therefore, many groups have developed attenuated derivatives of wild-type viruses specific for tumors by regulating those viral mechanisms necessary for infection of healthy cells and systems but dispensable for productive infection of tumors.…”

Section: Introductionmentioning

confidence: 99%

Development of transcriptionally regulated oncolytic adenoviruses

Hawkins

2005

Oncogene

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Studies of Adenoviruses (APC) in Volunteers

Cited by 76 publications

References 14 publications

Acute Respiratory Disease in Normal Volunteers Associated With Coxsackie a-21 Viral Infection. Iii. Response to Nasopharyngeal and Enteric Inoculation

Acute Respiratory Disease in Normal Volunteers Associated With Coxsackie a-21 Viral Infection. Iii. Response to Nasopharyngeal and Enteric Inoculation

Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

Development of transcriptionally regulated oncolytic adenoviruses

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