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Summary One hundred and four pediatric patientswith a history of repeated respiratory illnesses were inoculated with a hexavalent adenovirus vaccine. It failed to produce significant antibody response in a large proportion of the patients. Unless and until a large-scale controlled study shows statistically significant increases in antibody titer and decreases in respiratory illness attributable to the use of this vaccine, there is not sufficient evidence to justify its routine use in pediatrics.

THE ACUTE respiratory illnesses of man caused by viruses constitute one of the last great frontiers in infectious disease. It is not surprising, therefore, that much research effort has been expended in recent years to the cultivation of the causal agents in the laboratory and to the evaluation of their importance as disease-producing entities. The discovery in 1953 of the adenoviruses 1-3 represents the most significant advance in our knowledge of etiology of acute respiratory illnesses in man since the discovery of human influenza virus in 1933. The adenovirus discovery was a sequel to the renaissance of tissue culture for virus propagation which has since resulted in the recovery of additional new agents. Shortly after the initial recovery of the adenoviruses, it was shown that these viruses are a family of distinct immunologic types as determined by the neutralization technic 4-8 and that they share a common group-specific "soluble" complement-fixing antigen.1"4' 5, 9,10 It was also found that these viruses are a principal cause of acute respiratory illnesses among newly recruited military personnel.7 11-15 The respiratory illnesses caused by adenoviruses fall into the general category of the febrile catarrhs 16, 17 and into the specific syndromes of undifferentiated acute respiratory disease (ARD), nonstreptococcal exudative pharyngitis, atypical pneumonia unassociated with cold agglutinins, and pharyngoconjunctival fever.17-22 In extensive studies carried out at military camps it has been found 14, 23 that the adenoviruses may cause hospitalization of roughly 10 per cent of the entire basic trainee component of a training post during the year. During the winter months up to 90 per cent of all hospital admissions for acute respiratory illness in military recruit camps may be adenovirus cases.11-13, 15, 23 This causes great loss in military manpower, large costs for medical care, and serious disruption of the troop training program.23' 24

Background The acute respiratory illnesses caused by adenoviruses (RI-APC-ARD) 1-3 constitute a major problem in military medicine. These agents are the cause for the majority of cases of acute respiratory illness among new recruits in the Armed Forces. 4-8 By contrast, adenovirus-caused respiratory disease is relatively infrequent among the "seasoned" cadre, and this is true also of the adult civilian population. The respiratory illnesses caused by adenoviruses fall into the general syndromes of febrile catarrh, undifferentiated acute respiratory disease (ARD), nonstreptococcal exudate pharyngitis, atypical pneumonia unassociated with the development of cold agglutinins, and pharyngoconjunctival fever. 9-11 More commonly, these illnesses are referred to as catarrhal fever, grippe, acute pharyngitis, "severe colds," or virus pneumonia. The adenoviruses have not been associated etiologically with the common cold. 9,12 At least 14 distinct immunological types of adenovirus have been recognized up to the present. 13 Only three of these, however, namely, Types 4, 7, and 3

Summary Adenovirus vaccine potency estimates, based upon immune responses following multiple injections of fluid vaccine, were unreliable. As an alternative, a potency test based upon a single injection of vaccine with oil-adjuvant is described. In this test, no evidence of interference among components in multivalent vaccines was demonstrable. The test was responsive to potency changes in a stability study of this vaccine.

During the developmental period of the adenovirus vaccine, field trials of bivalent Types 4 and 7 vaccine conducted by the Army Medical Service in 1956 and 1957 resulted in 90% to 98% reduction in hospitalization due to adenovirus disease in recruits. During the respiratory disease season of 1960-1961, a standardized, commercially prepared, Types 4 and 7 vaccine was used at all recruit training stations. Preliminary results indicate that this vaccine was about 50% effective in reducing hospitalization resulting from adenovirus disease. It is evident from the earlier experience that, even though the commercial vaccine now being used is estimated to have saved the Army about $5,000,000 during the last respiratory disease season, there is an urgent requirement to make available adenovirus vaccine of greater antigenicity.

Earlier reports 1-5 from this laboratory described the development and evaluation in the field of a formalin-killed bivalent adenovirus 6-8 vaccine of monkey-kidney origin. The vaccine was prepared at the Walter Reed Army Institute of Research, and the evaluation consisted of a controlled field study conducted during the winter of 1956 in 624 newly inducted recruits at Fort Dix, N. J. The vaccine was highly effective, commencing one week after vaccination, and produced a 98% reduction in amount of adenovirus-caused respiratory illness. During the winter of 1957, a second controlled field evaluation of the vaccine was carried out among 8238 recruits stationed at Fort Leonard Wood, Mo. The vaccine employed in this trial was provided by Lederle Laboratories and was prepared under commercial conditions. This paper presents the findings in the field trial at Fort Leonard Wood, compares the potency values of the Lederle and Walter Reed vaccines, and presents data concerning