Protective effect of the F(ab')2 fragments of monoclonal antibodies to mouse hepatitis virus
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K Nakanaga1, K Yamanouchi, K Fujiwara
1Department of Animal Pathology, University of Tokyo.
Abstract:
The F(ab')2 fragments were prepared from three monoclonal antibodies (MAbs) reactive with either peplomer glycoprotein (E2) or nucleocapsid protein (NP) of a low-virulence mouse hepatitis virus (MHV), MHV-NuU. All the three MAbs could protect mice from challenge infection with virulent MHV-2, whereas only one of the anti-E2 MAbs was capable of neutralizing the virus in vitro. The F(ab')2 fragment of neutralizing anti-E2 MAb was shown to protect mice from challenge infection, but those of non-neutralizing anti-E2 and anti-NP MAbs were not protective.
Insights
Monoclonal antibodies targeting mouse hepatitis virus (MHV) proteins E2 or NP protected mice. However, only antibodies neutralizing the virus in vitro conferred protection via F(ab')2 fragments.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Mouse hepatitis virus (MHV) is a significant pathogen in murine models.
- Monoclonal antibodies (MAbs) are crucial tools for studying viral pathogenesis and developing therapeutics.
- Understanding antibody-mediated protection against MHV is essential for disease control.
Purpose of the Study:
- To investigate the protective efficacy of F(ab")2 fragments derived from MAbs against different MHV proteins.
- To determine the correlation between in vitro neutralization and in vivo protection against MHV infection.
- To elucidate the role of specific MHV viral components targeted by MAbs in conferring protection.
Main Methods:
- Preparation of F(ab")2 fragments from three MAbs targeting MHV peplomer glycoprotein (E2) and nucleocapsid protein (NP).
- Assessment of MAb protection in mice challenged with virulent MHV-2.
- Evaluation of in vitro viral neutralization capacity of the MAbs.
- Testing the protective efficacy of F(ab")2 fragments in vivo.
Main Results:
- All three MAbs conferred protection against MHV challenge infection in mice.
- Only one anti-E2 MAb demonstrated in vitro virus neutralization.
- The F(ab")2 fragment of the neutralizing anti-E2 MAb protected mice.
- F(ab")2 fragments from non-neutralizing anti-E2 and anti-NP MAbs did not provide protection.
Conclusions:
- In vitro neutralization activity is a key indicator for protective efficacy of anti-MHV antibodies.
- Targeting the peplomer glycoprotein (E2) with neutralizing antibodies is critical for protection against MHV.
- F(ab")2 fragments derived from neutralizing antibodies can effectively protect against MHV challenge infection.