No abstract

Lymphocytic choriomeningitis virus (LCMV) is the prototype of the family Arenaviridae and is associated with the natural reservoir, Mus domesticus (Md). It causes meningitis and a flu-like illness characterized by malaise, myalgia, retrorbital headache, and photophobia. This study presents the data obtained in a rodent and human serological study during 6 years (1998-2003) in the city of Rio Cuarto, Argentina. Antibodies anti-LCMV were sought by ELISA in rodents and humans. LCMV was found only in Md species in 9.4% of animals. The results also show some seasonal, no significant variations in the prevalence of the infection. Distribution of positive mice was not modified significantly by trapping sites, sex, or age of the animals. The prevalence of LCMV positive urban residents was found to be consistently low (1-3.6%) along the study period, with overage prevalence of 3.3% and values in males (4.6%) significantly higher than in females (2.6%) (P < 0.05). Seven of 432 pregnant women were found to be LCMV positive, but the absence of LCMV antibodies in the newborns demonstrated that the mothers were infected before pregnancy. This study is the first evidence on endemic LCMV in an Argentine city located outside the endemic area of Argentine hemorrhagic fever (AHF) and described the need to study other areas and increase awareness of this viral infection.

Neutralizing antibody (NT Ab) titers to Candid #1 (C#1) vaccine against Argentine hemorrhagic fever were studied for 2 years post-vaccination in 330 volunteers, to assess whether the kinetics and/or magnitude of this immune response is modified by previous infection with the arena viruses Junin (JUN) and lymphocytic choriomeningitis (LCM). A total of 160 volunteers received C#1, distributed as follows: without detectable pre-infection with arenaviruses (n = 54); with pre-existing antibodies to JUN (n = 55); with pre-existing antibodies to LCM (n = 51). The remaining 170 individuals received placebo. Levels of anti-JUN NT Ab displayed a trend in which titers increased with the virulence of the infecting strain, from C#1 (X = 49), through subclinical JUN infection (X = 229), vaccination following subclinical infection (X = 367) to JUN clinical infection (X =773). It was also found that the mean titer of NT Ab to C#1 did not vary significantly during 2 years of study and was: a) significantly lower than that elicited by wild strains of JUN, both clinical and subclinical infections (p < 0.01); b) significantly increased the titers of pre-existing anti-JUN Ab (p < 0.01); and c) was not modified by pre-existing anti-LCM Ab (p > 0.05). These data indicate that the immune response to C#1 boosts pre-existing immunity to JUN virus and is not changed by previous experience with LCM virus.

Different proportions of IgG subclasses have previously been reported to distinguish the immune response elicited by primary and recurrent viral infections, as well as viral vaccines. The goal of this study was to study the IgG subclasses composition in the immune response of patients with Argentine hemorrhagic fever, and vaccinees with Candid #1 strain of Junin virus. Twenty-four individuals inoculated with Candid #1 vaccine and 67 patients with Argentine hemorrhagic fever were studied. Blood samples were drawn at 30, 60, and/or 180 days post-inoculation with Candid #1 and 30, 60, and 90 days after clinical onset of the disease. Specific anti-Junin virus IgG subclasses were titrated with specific human monoclonal antibody fluorescence isothiocyanate conjugate (FITC) by immunofluorescent assay (IFA). IgG(1) anti-Junin virus was found in every subject studied and IgG(3) was also detected in some patients with a severe form of Argentine hemorrhagic fever. IgG(2) and IgG(4) were not detected in any serum sample studied. The mean titer of specific IgG(1) in vaccinees was significantly lower than in patients with Argentine hemorrhagic fever (P < 0.05), but no difference was found between mild and severe cases of the disease (P > 0.05). The results of this study demonstrated a central role of IgG(1) in human recovery from infection with every strain of Junin virus, an observation stressed by the immune response to Candid #1 vaccine, which resulted in no difference in IgG subclasses composition from that found in mild cases of Argentine hemorrhagic fever.

The Mammarenavirus genus of the Arenaviridae family includes several members that cause severe hemorrhagic fevers associated with high morbidity and mortality rates, for which no FDA-approved vaccines and limited therapeutic resources are available. We provide evidence demonstrating the specific involvement of the TCRV S 5′ noncoding sequence adjacent to the viral promoter in replication.