Induction of protective immunity in a syrian hamster model against a cytopathogenic strain of andes virus

Abstract

Andes virus (ANDV) is responsible for the Hantavirus Pulmonary Syndrome cases in Argentina and neighboring countries, with moderate to high case-fatality rates. ANDV has some particular features, which make it unique among other members of the Hantavirus genus such as person-to-person transmission and causing a disease similar to Hantavirus Pulmonary Syndrome in the hamster as an animal model. The kinetics of replication in Vero E6 cells of an ANDV strain isolated in Argentina, called Andes/ARG, was studied. Cytopathic effect and the formation of clear plaques were observed and therefore Andes/ARG could be quantified by classic plaque assay. The Andes/ARG strain was found to be highly lethal in Syrian hamsters allowing experiments to demonstrate the protective potential of vaccines. A recombinant nucleocapsid protein of ANDV induced a long lasting antibody response and protective immunity against a homologous challenge, but to a lower extent against heterologous challenge by the Seoul virus.

The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster

“…To have elicited a specific antibody response, the virus was clearly detected, but interestingly, detection has no consequence in the case of SNVp5. It is possible that the presence of virus‐specific antibodies has no biological significance after the establishment of an infection, as immunization of hamsters with recombinant ANDV‐N renders them resistant to ANDV‐induced disease, but anti‐N antibodies given to deer mice concomitantly with SNV challenge do not have an effect on virus replication in tissues . In the former study, it is possible that the mechanism of protection upon immunization is cell‐mediated immunity, and the actual presence of antibody might be inconsequential.…”

“…It is possible that the presence of virus-specific antibodies has no biological significance after the establishment of an infection, as immunization of hamsters with recombinant ANDV-N renders them resistant to ANDV-induced disease, but anti-N antibodies given to deer mice concomitantly with SNV challenge do not have an effect on virus replication in tissues. 36,37 In the former study, it is possible that the mechanism of protection upon immunization is cell-mediated immunity, and the actual presence of antibody might be inconsequential. In the natural reservoirs of hantaviruses, high levels of antibody are detected, despite viral persistence.…”

The Syrian hamster model of hantavirus pulmonary syndrome

“…To date, two isolates of ANDV have been shown to cause HPS disease in hamsters without prior host adaptation (Hooper et al, 2001; Martinez and Padula, 2012). Besides ANDV, only MAPV has been shown to cause disease in hamsters (Milazzo et al, 2002).…”

“…However, in South America the incidence of HPS is higher and multiple cases of HPS in the same temporal and geographical proximity are more common which suggests a vaccine could be beneficial. To date, the ANDV hamster model has been utilized in at least five vaccine studies which have provided unique insight into the development of hantavirus vaccines (Brown et al, 2011; Custer et al, 2003; Hooper et al, 2006; Martinez and Padula, 2012; Safronetz et al, 2009). …”

“…In partial support of this, monoclonal antibodies specific for HTNV nucleoprotein were shown to prevent lethal HTNV infection in new-borne mice (Yoshimatsu et al, 1996). Recently, a study demonstrated that it was possible to protect Syrian hamsters from lethal HPS caused by ANDV by vaccinating with a purified NP antigen (Martinez and Padula, 2012). …”