A review of immunization against human rickettsial diseases

Abstract

1. 1. Recovery from a rickettsial infection is accompanied by the development of considerable immunity; therefore, protective vaccination is theoretically possible. 2. 2. In practice, difficulties are encountered because living vaccines may be dangerous, and dead rickettsias have relatively little immunizing power. 3. 3. These difficulties might be overcome by using vaccines of living but attenuated organisms or relatively large numbers of killed organisms. 4. 4. Large numbers of organisms are not conveniently obtainable as rickettsias will not grow in ordinary media. They can, however, multiply enormously in appropriate arthropods, and Parker and Spencer utilized this to prepare a satisfactory killed vaccine against Rocky Mountain spotted fever from phenol-formolized suspensions of ground-up infected ticks. 5. 5. Weigl prepared an effective typhus vaccine by emulsifying in phenolsaline the heavily infected intestines of artificially infected lice. By Weigl's technique, Mosing prepared a specific vaccine which he thought had some action against a trench fever-like disease. The labour involved limits production and Weigl's vaccine has also been criticized on the general ground that killed vaccines only give feeble, restricted and short-lived immunity. 6. 6. Infections can also be developed in laboratory animals and early attempts were made to use infected tissue suspensions as vaccines, but the small yields of rickettsias when killed failed to vaccinate satisfactorily. 7. 7. As living organisms, although attenuated, might give rise to accidental infections, the danger in typhus was diminished by using the relatively benign murine virus which, owing to cross immunity between it and classical typhus, can when living immunize against either infection. Although considerable cross immunity exists between classical and murine typhus, the enfeebled protective power of killed rickettsias is manifest in a much stricter specificity of the respective killed vaccines in the two diseases. 8. 8. Blanc and his colleagues rendered living murine virus from infected guineapigs innocuous by treating it with ox-bile; the virus is very unstable and a modification has been introduced whereby dried infected flea faeces, which retain their virulence for long periods, are used as the source of virus for the vaccine. Nicolle and Laigret attenuated a murine virus from guineapigs and rats by drying and coating it with egg yolk and olive oil; Laigret and Durand have introduced a further modification using mouse-brain passage virus. These vaccines normally produce only inapparent infections, reactions of vaccinial typhus being rare. Nevertheless, in certain circumstances, such reactions may not be negligible. 9. 9. Zinsser, disbelieving the reliability of controlled attenuation, attempted to obtain sufficient quantities of rickettsias for killed vaccines from animals heavily infected by having their resistance artificially lowered. 10. 10. Thus Zinsser and Castenada, with murine virus in rats irradiated with X-rays, obtained peritoneal accumulations of virus sufficiently rich to prepare a practical phenolized vaccine. Its protection against classical typhus was, however, poor, nor could they get satisfactory yields of classical virus from irradiated rats. 11. 11. Efforts are now being made to produce vaccines of various rickettsias grown in tissue cultures, and in the yolk sac and tissues of developing chicks; other experiments seek to obtain sufficient yields from animals by simpler methods. Durand and Sparrow recently reported an important technical advance whereby intranasal instillation of typhus viruses into etherized white mice results in a rapid and massive pulmonary infection, from which rich cell-free suspensions of rickettsias can be prepared. Utilizing this, Durand and Giroud have recently prepared mouse lung vaccines against classical typhus. 12. 12. Sera from convalescents, from those vaccinated or from animals artificially immunized, may confer good but brief passive immunity against rickettsial diseases; the curative action in declared infections is less certain. Combined sero-vaccination has been suggested to give typhus contacts immediate protection followed by active immunity.