Genotype-specific and Cross-reactive Neutralizing Antibodies Induced by Dengue Virus Infection: Detection of Antibodies with Different Levels of Neutralizing Activities Against Homologous and Heterologous Genotypes of Dengue Virus Type 2 in Common...

Overview

Journal Virol J

Publisher Biomed Central

Specialty Microbiology

Date 2018 Mar 29

PMID 29587780

Citations 3

Authors

Nor Azila Muhammad Azami

Meng Ling Moi

Yasushi Ami

Yuriko Suzaki

Chang-Kweng Lim

Satoshi Taniguchi

Masayuki Saijo

Tomohiko Takasaki

Ichiro Kurane

Affiliations

Soon will be listed here.

Abstract

Background: A vaccine against all four dengue virus (DENV) serotypes includes the formulation of one genotype of each serotype. Although genetic similarities among genotypes within a serotype are higher as compared to those among serotypes, differences in the immunogenicity of the included genotypes would be a critical issue in maximizing successful dengue vaccine development. Thus, we determined the neutralizing antibody responses against three genotypes of dengue virus serotype 2 (DENV-2), namely Cosmopolitan, Asian I, and Asian/American, after primary and secondary inoculation with DENV-2 in a dengue animal model, the common marmoset (Callithrix jacchus).

Methods: A total of fifty-four plasma samples were obtained from thirty-four marmosets that were inoculated with clinically-isolated DENV strains or DENV candidate vaccines, were used in this study. Plasma samples were obtained from marmosets after primary inoculation with DENV-2 infection, secondary inoculation with homologous or heterologous genotypes, and tertiary inoculation with heterologous DENV. Neutralizing antibody titers against DENV-2 (Cosmopolitan, Asian I, and Asian/American genotypes) and DENV-1 were determined using a conventional plaque reduction neutralization assay.

Results: In marmosets that were inoculated with the Cosmopolitan genotype in primary infection, neutralizing antibody neutralized 3 genotypes, and the titers to Asian I genotype were significantly higher than those to homologous Cosmopolitan genotype. After secondary DENV-2 infection with heterologous genotype (Asian I in primary and Asian/American in secondary), neutralizing antibody titers to Asian/American genotype was significantly higher than those against Cosmopolitan and Asian I genotypes. Following tertiary infection with DENV-1 following DENV-2 Asian I and Cosmopolitan genotypes, neutralizing antibody titers to Asian/American were also significantly higher than those against Cosmopolitan and Asian I genotypes.

Conclusion: The present study demonstrated that different levels of neutralizing antibodies were induced against variable DENV-2 genotypes after primary, secondary and tertiary infections, and that neutralizing antibody titers to some heterologous genotypes were higher than those to homologous genotypes within a serotype. The results indicate that heterogeneity and homogeneity of infecting genotypes influence the levels and cross-reactivity of neutralizing antibodies induced in following infections. The results also suggest that certain genotypes may possess advantage in terms of breakthrough infections against vaccination.

Citing Articles

Efficacy of an inactivated Zika vaccine against virus infection during pregnancy in mice and marmosets.

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PMID: 35087081 PMC: 8795414. DOI: 10.1038/s41541-021-00426-0.

Genotype-Dependent Immunogenicity of Dengue Virus Type 2 Asian I and Asian/American Genotypes in Common Marmoset (: Discrepancy in Neutralizing and Infection-Enhancing Antibody Levels between Genotypes.

Azami N, Moi M, Ami Y, Suzaki Y, Taniguchi S, Tajima S Microorganisms. 2021; 9(11).

PMID: 34835327 PMC: 8618970. DOI: 10.3390/microorganisms9112196.

Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys.

Azami N, Takasaki T, Kurane I, Moi M Pathogens. 2020; 9(4).

PMID: 32230836 PMC: 7238212. DOI: 10.3390/pathogens9040247.

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