About: Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants

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About: Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants
Creator	Goutama, Michael Ho, Hui-Ting Hongliang, Qian Kwang, Jimmy Prabakaran, Mookkan Prabhu, Nayana Qiang, Jia Meng, Tao
Source	Medline; PMC
abstract	BACKGROUND: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. METHODS/PRINCIPAL FINDINGS: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy. CONCLUSIONS/SIGNIFICANCE: Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.
has issue date	2009-05-22(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0005672
bibo:pmid	19478856
has license	cc-by
sha1sum (hex)	920282c7a0656a43143be9b656b36367cf871c08
schema:url	https://doi.org/10.1371/journal.pone.0005672
resource representing a document's title	Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants
has PubMed Central identifier	PMC2682562
has PubMed identifier	19478856
schema:publication	PLoS One
resource representing a document's body	covid:920282c7a0656a43143be9b656b36367cf871c08#body_text
is schema:about of	named entity 'MUTANTS' named entity 'Antibodies' named entity 'Therapy' named entity 'INFECTION' named entity 'PREVENTS' named entity 'LETHAL' named entity 'ESCAPE' named entity 'STRAINS' named entity 'DRUGS' named entity 'VIRUSES' named entity 'SINGLE' named entity 'HUMAN' named entity 'IS A' named entity 'DIFFERENT' named entity 'IMMUNE' named entity 'RESISTANT TO' named entity 'BUT' named entity 'BROAD' named entity 'MUTANTS' named entity 'THERAPY' named entity 'PANDEMIC' named entity 'FACT' covid:arg/920282c7a0656a43143be9b656b36367cf871c08 named entity 'COMBINATION THERAPY' named entity 'GIVEN' named entity 'USING' named entity 'CHIMERIC' named entity 'FORMATION' named entity 'CONTROL' named entity 'RANGE' named entity 'EFFECTIVE' named entity 'VIRAL' named entity 'PREVIOUS' named entity 'POTENTIAL' named entity 'POSSIBILITY OF' named entity 'STRATEGIES' named entity 'H5N1' named entity 'INFECTION' named entity 'PROPHYLAXIS' named entity 'BACKGROUND' named entity 'MONOCLONAL ANTIBODIES' named entity 'MICE' named entity 'ESCAPE' named entity 'H5N1' named entity 'MAB' named entity 'RECENT' named entity 'STUDIES' named entity 'anti-viral' named entity 'prophylaxis' named entity 'immune' named entity 'fact' named entity 'But' named entity 'H5N1' named entity 'Lethal' named entity 'mAbs' named entity 'H5N1' named entity 'clades' named entity 'Equine' named entity 'Arg' named entity 'double dose' named entity 'polyclonal antibodies' named entity 'BSL-3' named entity 'influenza' named entity 'cloned' named entity 'fluorescein isothiocyanate' named entity 'phylogenetic' named entity 'PBS' named entity 'lungs' named entity 'viral infection' named entity 'human clinical trials' named entity 'recombinant antibody' named entity 'mAbs' named entity 'Arg' named entity 'mAbs'

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