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Updated: Jul 19, 2026
Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Isolation of monoclonal antibodies-escape variant of dengue virus serotype 1
S K Chua1, S Selvanesan, B Sivalingam
1Hospital Tengku Ampuan Rahimah, Jalan Banting, Klang 41200, Malaysia. chuakawbing@yahoo.com.sg
Introduction:
During an outbreak from December 2004 to March 2005, 138 isolates of dengue virus were prospectively obtained from acute-phase serum samples of 1,067 patients with the provisional clinical diagnosis of acute dengue illness admitted to the adult wards of Hospital Tengku Ampuan Rahimah, Klang, Malaysia. Of the 138 dengue virus isolates, 87, 11, 24 and 3 were typed as dengue serotypes 1, 2, 3 and 4, respectively, by a commercial dengue virus typing kit using monoclonal antibodies (Mab). 13 dengue virus isolates could not be assigned to any specific serotype by serotyping Mab and molecular typing using dengue-type specific molecular typing primer pairs. We report the associated clinical features and limited molecular genetics of this Mab-escape dengue virus variant.
Methods:
Limited molecular characterisation of the Mab-escape dengue virus variants with respect to a few concurrently isolated dengue serotype 1 virus was performed by reverse transcriptase polymerase chain reaction (RT-PCR), followed by nucleic acid sequencing of the 500-bp dengue virus partial genomic capsid-PreM fragment.
Results:
The aligned nucleic acid sequence of RT-PCR products showed that these Mab-escape variants were of identical nucleic acid sequence, and shared the highest sequence homology (99 percent) with dengue virus serotype 1 (GeneBank accession No. AB178040) isolated from a Japanese patient in 2004. Though these Mab-escape dengue virus variants were noted to replicate to a 2-log higher titre than the current circulating dengue virus serotype 1, there was no significant difference between these variants and the currently circulating dengue virus serotype 1 with respect to disease severity (dengue fever versus dengue haemorrhagic fever) and clinical features.
Conclusion:
There was no significant difference in the proportion of patients developing dengue haemorrhagic fever following acute infection by Mab-escape dengue virus 1 variant in comparison with infection by the conventional dengue virus 1. Similarly, there was no significant difference in the pattern of clinical presentations following acute infection by the two different strains of virus.
Insights
A novel dengue virus variant, resistant to antibody detection, was identified during a Malaysian outbreak. This dengue virus 1 variant showed higher replication but did not alter disease severity or clinical presentation compared to standard dengue virus 1.
Area of Science:
- Virology
- Molecular Biology
- Epidemiology
Background:
- A dengue virus outbreak in Malaysia (December 2004–March 2005) yielded 138 isolates from 1,067 patients.
- A subset of 13 isolates exhibited resistance to standard serotyping by monoclonal antibodies (Mab) and molecular typing.
- These Mab-escape variants were characterized to understand their genetic and clinical implications.
Purpose of the Study:
- To investigate the clinical features and molecular genetics of Mab-escape dengue virus variants.
- To compare the pathogenicity and clinical presentation of Mab-escape dengue virus 1 with conventional dengue virus 1.
Main Methods:
- Reverse transcriptase polymerase chain reaction (RT-PCR) was used for molecular characterization.
- Nucleic acid sequencing of the 500-bp capsid-PreM fragment was performed.
- Sequence homology and viral replication titres were analyzed.
Main Results:
- Mab-escape variants displayed identical nucleic acid sequences with 99% homology to dengue virus serotype 1.
- These variants replicated to a 2-log higher titre than contemporary dengue virus serotype 1.
- No significant differences in disease severity (dengue fever vs. dengue hemorrhagic fever) or clinical features were observed.
Conclusions:
- Mab-escape dengue virus 1 variants do not increase the risk of developing dengue hemorrhagic fever.
- Clinical presentations following infection with Mab-escape variants are similar to those of conventional dengue virus 1.
- The emergence of antibody-resistant dengue virus strains warrants further surveillance.
