The evidence herein presented indicates that anti-typhus vaccines of the inactivated type are of well-established value. While most of the evidence relates to Cox-type vaccines of yolk-sac origin, the conclusions to be drawn probably are also applicable to potent vaccines derived from infected lice or animal lungs. It is clear that adequate primary immunization will greatly modify such disease as may occur and will virtually eliminate fatality. The degree of reduction in morbidity remains undetermined but is undoubtedly significant. Data as to duration of real immunity after primary immunization do not exist (our small challenge experiments failed to reveal solid immunity at 9 and 21 months post-vaccination). However, serologic evidence indicates that administration of single booster inoculum from 9 months to as long as 6 years later results in effective restimulation of immunity. While repeated booster inocula will undoubtedly serve to maintain a good level of immunity, an appropriate schedule of inoculations has not yet been worked out.
Use of a living rickettsial vaccine offers obvious possible advantages in that a single inoculation should result in solid and long-lasting immunity. Nearly all previous efforts to use living rickettsiae involved, basically, the use of minute doses of agents of unmodified virulence, minute because of dilution or partial inactivation. The concensus is that such vaccines, when given to non-immune persons, either failed to infect and to immunize, or produced unmodified, inoculation typhus.
The evidence available with respect to strain E indicates that it is indeed a strain of R. prowazeki of greatly reduced virulence for man. Its primary safety is attested by its use in upwards of 17,000 persons with no single known instance of truly serious illness resulting. Further, it is unlikely that it could be picked up and spread by lice because of its apparent inability to invade the blood stream. Admittedly, reactions do follow the use of strain E. However, there is a dose range (4.0 to 5.5 log E.I.D.) which induces both a tolerable level of reactions and a satisfactorily uniform immediate seroimmune response. Available evidence, with respect to both seroimmunity and ability to resist virulent challenge, indicates that, while immunity induced by strain E infection may not be fully comparable to that following natural infection, it is solidly effective for at least 3 years and probably considerably longer.
There are, however, some problems remaining. That actual infection of man does occur is suggested on clinical grounds by the development of regional adenitis and of reactions of the delayed type. It also is suggested by the fact that the minimum immunizing dose of formol-inactivated rickettsiae is 2.5 logs greater than that of living strain E (Everritt et al., 1954). However, knowledge as to the fact and possible sites of persistence of the agent in man should be sought. Also, while strain E-induced immunity seems superior to that following primary immunization with Cox-type vaccine, a comparison also should be made with that in persons given in addition a booster inoculum of inactive vaccine. Again, while the considerable field use of the vaccine in Peru testifies to its practical applicability under field conditions, criteria as to minimum infectivity, recommended dosage and expiration dates of production lots of vaccine remain to be defined. Finally, although the results of the challenge experiments offer much promise as to effectiveness, there remains the crucial problem of obtaining definitive data as to the effectiveness of strain E vaccine in preventing the natural occurrence of disease.