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The results of a comparative study of different routes of inoculation of simian hemorrhagic fever (SHF) virus to Macaca monkeys are presented as well as the results of virological examinations of sick animals. Only the parenteral route of inoculation has been found to be effective. After virus penetration, a long-term viremia and generalization of the infection are observed. The virus is found in the brain, the spinal cord and bone marrow, the spleen, the liver, the kidneys, the cerebrospinal fluid, the urine and nasopharyngeal washings. By the fluorescent antibody technique the virus-specific antigen is demonstrated in the capillary endothelium, neurons and glial cells of the brain, and in the reticulo-endothelial and macrophagal elements of parenchymatous organs.

Cross-protection between Junin virus and five other Tacaribe complex viruses and the serological response of guinea pigs inoculated with Tacaribe virus are reported here. Previous infection with Tamiami or Pichinde viruses significantly delayed guinea pig deaths. A 58% survival rate was found among animals immunized with three doses of Amapari virus, while guinea pigs inoculated with one dose of Machupo or Tacaribe virus were fully protected against Junin virus. Neutralization tests performed in serum samples of guinea pigs immunized with five doses of Tacaribe virus showed that they developed monologous and heterologous neutralizing antibodies.

Arenaviruses are known to show antigenic relationships in the complement-fixation (CF) and fluorescent antibody tests but not in the neutralization test. The humoral response to some of the arenaviruses is characterized by a dissociation between the antibodies determined by the CF test and those determined by the neutralization test and also by its late appearance following natural infection. Investigations are reported showing that, as regards the CF test, Junin, Machupo, Amapari, and Tacaribe viruses are closely related, while LCM and Lassa viruses are distantly related to each other and to the remaining viruses in the group. Studies by agar gel diffusion and precipitation have shown complete specificity except among viruses that are very closely related in the CF test. Observations with sera from persons infected with Lassa fever virus show that CF antibodies rarely appear before the 18th day after onset; they can persist, with diminishing titres, for up to 6 years.

Rabbit anti-mouse thymocyte serum (ATS) administrated as late as 7 days after infection suppressed host cell-mediated responsiveness to intracerebrally injected Junín virus, thereby diminishing the morbility and mortality of this infection. It did not affect either the humoral antibody response or the virus titer in brain. This findings suggest that: a) in mouse brain cells, Junín virus infection is basically non-cytopathic: b) cell-mediated immunity is responsible for morbility and mortality and does not clear up virus from brain as in other viral encephalitides; and c) ATS may be of therapeutic interest by suppressing or diminishing the cell-mediated response to Junín virus.

Passive immunity, naturally acquired from immune mothers or artificially induced by the administration of homologous hyperimmune serum, conferred on suckling mice a high degree of resistance against infection with Junín virus. Maternal antibodies in the circulating blood of the young were not detectable in the first days after birth, but rised rapidly from the 8th to the 20th day of lactation. By cross-foster nursing experiments it was shown that the greater part of the transmission of passive immunity occurred after birth, although there was transmission of a significant, though small part, before birth. The virus passage from mothers to offspring was excluded, since Junín virus was not recovered from brains, livers, spleens and kidneys of uninfected young, born from infected mothers.

A Crimean hemorrhagic fever-Congo (CHF-C) virus antibody survey was carried out in Iran with sera from man and several animal species; this survey was done by means of agar gel diffusion precipitation (AGDP) test with the following results (percent positive of number tested): men, 13% of 351; sheep, 38% of 728; goats, 36% of 135; cattle, 18% of 130; camels, 0% of 157; small mammals, 3% of 274. A number of sera were tested by complement-fixation (CF), neutralization (N), and hemagglutination-inhibition (HI) tests in addition to the AGDP test. A good correlation was found in the results with 105 sera tested by AGDP, HI, and N, with approximately 70% to 75% positive in all three tests; by CF, only 20% were positive. Of 55 human sera, of which 15 could be tested by N test, about half were positive by AGDP and only 10% by HI at low titers; none was positive by N and CF tests. These results suggest that any one of the three serological tests (N, HI, and AGDP) can be used to survey the antibody prevalence in sera from domestic animals; the CF test, not unexpectedly, was less suitable. Our results, however, are inconclusive in regard to the human sera.

The indirect haemagglutination test has been developed for use with LCM and Tacaribe viruses employing antibody-sensitized erythrocytes. Both in this test and in the indirect haemagglutination inhibition test cross-reactions between LCM and Tacaribe viruses were revealed. This opens new perspectives for group and species identification of arenaviruses.

A limited but definite need exists for vaccines against Lassa, Junin, and Machupo viruses. Medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. To date little work has been done on inactivated vaccines for these viruses. A live attenuated Junin vaccine has been tested successfully in more than 600 persons, and a high-passage Machupo virus strain has protected rhesus monkeys against lethal infection produced by a homologous field strain.Work has been initiated on possible heterologous protection induced by infection or antigenic stimulation with arenaviruses not pathogenic for man. Crucial for the eventual development of effective vaccines are the construction of more maximum security laboratories and the further elucidation of the experimental and natural biology of the agents in lower animals and man.