PROTECTIVE ACTION OF CERTAIN CHEMICALS AGAINST INFECTION OF MONKEYS WITH NASALLY INSTILLED POLIOMYELITIS VIRUS.
In the present investigation evidence was obtained indicating that nasal instillations of suitable concentrations of sodium alum or tannic acid induce in Macacus rhesus monkeys resistance to the development of poliomyelitis when the virus is introduced by the nasal route. It was found that apparently different concentrations of these chemicals are required to exert this type of protective effect in different hosts or against different viruses, for while mice are readily protected against nasal infection with equine encephalomyelitis virus by 0.5 per cent solutions of tannic acid or alum (7), monkeys require at least 3 per cent solutions to become resistant against poliomyelitis. Experiments designed to elucidate the development of this refractory state in monkeys indicate that it is a result of the action of these chemicals not upon the virus but rather upon the tissues of the host (probably the olfactory mucosa); further evidence in favor of this hypothesis may be found in the observation that several days of treatment are required before resistance is induced. While one nasal instillation a day for 3 days proved effective when additional treatments were given on the days of virus administration, there was no protection against infection when the virus was given 48 and 96 hours after the last treatment. The resistance which was demonstrable when the virus was instilled intranasally on the 4th and 6th days after the beginning of treatment was also found to be present a week later when the treatments were given daily, indicating that the refractory state can be maintained in this manner. It was observed, however, that monkeys which were given nasal instillations of alum or tannic acid for 5 days or more may retain the resistance they acquired for 1 or 2 months without any additional treatment (Table V); thus, of 15 refractory monkeys retested after 1 month, 11 were still resistant; seven of 15 monkeys were refractory when retested after 2 months, while only one of 11 failed to develop poliomyelitis after an interval of 3 months. These last results suggest that to maintain such a refractory state over a period of months it may be necessary to employ daily instillations only for about a week, with subsequent repetitions at intervals of several days or a week. An experiment performed to determine the effect of beginning alum treatment soon after, rather than before, the virus is administered, indicated that there is no danger from a possible early or primary effect enhancing the invasiveness of the virus. One cannot state with any certainty, however, whether or not in some of the monkeys so treated the development of poliomyelitis is inhibited or prevented. Finally, it should be stressed that treatment with alum or tannic acid either completely prevented the disease in monkeys, or else was entirely without effect. It is therefore not surprising that no evidence was obtained of development of specific, active immunity in monkeys rendered refractory by chemical treatment. As far as could be ascertained, the nasal instillation of tannic acid or alum in man proved thoroughly innocuous beyond some local irritation for a short time. The desirability of testing this procedure as an aid in the prevention of poliomyelitis in man during the months of greatest incidence or during epidemics is quite apparent. In conclusion, there may be broader implications in this approach to the prevention of certain infectious diseases transmitted naturally or experimentally by way of the nose. It seems desirable to make studies with other viruses transmitted by the nasal route, including those of influenza and the common cold. The evidence obtained in the present study that the chemically induced refractory state may persist in a large number of monkeys for a month or two after treatment over a period of 5 days or more, suggests that studies on individuals who are subject to frequent attacks of common cold may perhaps be profitable.
Laboratories of The Rockefeller Institute for Medical Research.
A B
AB
Sabin
P K
PK
Olitsky
H R
HR
Cox