Page 39 - ICGES Libro de Resúmenes MAC

Resumen de Conferencias Internacionales (CI)

NEW THERAPEUTIC TOOLS FOR ANDES HANTAVIRUS
CI­04 INFECTION

Maria I. Barria , Jose L. Garrido 1,2, Joseph Prescott , Felipe Bravo , Mario
1
3
1
4
Calvo , Brandi N. Williamson , Heinz Feldmann 5
5
1 Faculty of Biological Science, Department of Microbiology, Center of
Biotechnology, Universidad de Concepción, Chile. Ichor Biologics LLC, New
2
York, USA. Comparative Immunology of Risk Group­4 viruses, Center for
3
Biological Threats and Special Pathogens, Robert Koch Institute, Germany.
4 Vnstitute of Medicine, Universidad Austral de Chile, Chile. Laboratory of
5
Virology, National Institute of Allergy and Infectious Diseases, National Institutes
of Health, Rocky Mountain Laboratories, USA.
Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes hantavirus
(ANDV) is a severe disease that can progress to hypotension, pulmonary failure,
and cardiac shock, which results in around 36% case­fatality rate in humans.
Currently, there is no specific treatment or vaccine; however, several studies
have indicated that generation of neutralizing antibody responses correlates with
survival of HCPS. In this context, the immunological profile present in ANDV
survivors have not been well characterized and may be an important source of
valuable information to advance in future treatments.The goal of our research is
to study the immunological signature in ANDV infection and develop tools to
isolate human monoclonal antibodies (mAbs) against ANDV hantavirus.
Recombinant mAbs isolated from a subject previously infected with ANDV were
cloned, produced and characterized. Two mAbs, JL16 and MIB22, recognized
ANDV­GP and neutralized ANDV using pseudoviral particles and full replicative
virus. In addition, our data suggest that both mAbs bind different regions on the
ANDV­GP and that mAb JL16 posses a higher relative affinity than MIB22. For
the in vivo protection experiments, Syrian hamsters were challenged with ANDV
and administrated with an isotype control or a combination of two mAbs.
Hamsters were monitored daily for signs of disease. Survivors were euthanized
and sera and lung were collected for analysis. We examined the post­exposure
efficacy of the mAbs in a Syrian hamster model of ANDV­induced HCPS, and a
combination of both mAbs protected 100% of animals from a lethal challenge
even when the Ab cocktail was administrated 5+9 days post­infection.
Interestingly, when mAbs were administered at latter stages of infection, on day
8+10 post­infection, both mAbs protected animals 50% after a lethal challenge.
This data suggests that the combination of JL16 and MIB22 mAbs may be an
effective therapy for HCPS even in the latter stages of infection.

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