Lymphocytic choriomeningitis, or LCM, is a rodent-borne viral infectious disease that presents as aseptic meningitis (inflammation of the membrane, or meninges, that surrounds the brain and spinal cord), encephalitis (inflammation of the brain), or meningoencephalitis (inflammation of both the brain and meninges). Its causative agent is the lymphocytic choriomeningitis virus (LCMV), a member of the family Arenaviridae that was initially isolated in 1933. Although LCMV is most commonly recognized as causing neurological disease, as its name implies, infection without symptoms or mild febrile illnesses are common clinical manifestations. Additionally, pregnancy-related infection has been associated with congenital hydrocephalus, chorioretinitis, and mental retardation.
The primary host is the common house mouse, Mus musculus. Infection in house mouse populations may vary by geographic location; about 5% of mice throughout the United States carry LCMV. The virus is found in the saliva, urine, and feces of infected mice. Infected mice carry LCMV and shed it for the duration of their lives without showing any sign of illness. Other types of rodents, such as hamsters, are not the natural reservoirs but can become infected with LCMV from wild mice at the breeder, in the pet store or home environment. Humans are more likely to contract LCMV from house mice, but infections from pet rodents have also been reported.
Individuals become infected with LCMV after exposure to fresh urine, droppings, saliva, or nesting materials. Transmission can also occur when these materials are directly introduced into broken skin, the nose, the eyes, or the mouth, or presumably, via the bite of an infected rodent. Person-to-person transmission has not been reported, with the exception of vertical transmission from infected mother to fetus. Recent investigations indicate that organ transplantation may also be a means of transmission (CDC - LCMV).
Ifnar-/- vaccinated with propagation-deficient rLCMV vector expressing ovalbumin are protected from a challenge with the aggressive LCMV Arm and LCMV Clone 13. (Krolik et al., 2021)
g.
Mouse Response
Vaccination Protocol:
Age and sex-matched animals were vaccinated with 1x10^6 pfu of rLCMV-OVA. Wt or Ifnar-/- mice were used. (Krolik et al., 2021)
Immune Response:
In wt mice, induction of viral NP396 specific CD8+ T cells peaked at day eight and two weeks after vaccination for OVA257. In Ifnar-/-, T cell induction was delayed but reached equally high frequencies of antigen-specific CD8+ T cells by day 16 for the nucleoprotein and by day 30 for the vaccine antigen ovalbumin. (Krolik et al., 2021)
Challenge Protocol:
rLCMV-immunized wt or Ifnar-/- mice were challenged with low dose (200 pfu) or high dose (1x10^5 pfu) LCMV Arm (LCMV strain Armstrong). (Krolik et al., 2021)
Efficacy:
Immunized wt mice showed a sterile protection even after a high dose challenge. Ifnar-/- contained a low dose LCMV Arm challenge. Immunized Ifnar-/- receiving a high dose of LCMV Arm were partially protected, i.e. spreading of virus was pre- vented as virus remained below the detection limit in the liver. (Krolik et al., 2021)
h.
Mouse Response
Vaccination Protocol:
Age and sex-matched animals were vaccinated with 1x10^6 pfu of rLCMV-OVA. Wt or Ifnar-/- mice were used. (Krolik et al., 2021)
Immune Response:
In wt mice, induction of viral NP396 specific CD8+ T cells peaked at day eight and two weeks after vaccination for OVA257. In Ifnar-/-, T cell induction was delayed but reached equally high frequencies of antigen-specific CD8+ T cells by day 16 for the nucleoprotein and by day 30 for the vaccine antigen ovalbumin. (Krolik et al., 2021)
Challenge Protocol:
rLCMV immunized wt and Ifnar-/- mice were infected with 200 or 1x10^5 pfu of LCMV Cl13. (Krolik et al., 2021)
Efficacy:
Vaccinated wt mice controlled viral dissemination. rLCMV vaccinated Ifnar-/- showed a significantly reduced viral titer compared to unvaccinated controls in a low dose challenge with LCMV Cl13. rLCMV vectors can protect Ifnar-/- from a low dose challenge with the highly aggressive LCMV Cl13. (Krolik et al., 2021)
2. Lymphocytic choriomeningitis virus DNA vaccine pCMV-NP
