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 marmosets (Callithrix jacchus).

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.

• Authors: Nor Azila Muhammad Azami, Meng Ling Moi, Yasushi Ami, Yuriko Suzaki, Chang-Kweng Lim, Satoshi Taniguchi, Masayuki Saijo, Tomohiko Takasaki, Ichiro Kurane
• Journal: Virology journal (Virol J) Vol. 15 Issue 1 Pg. 51 (03 27 2018) ISSN: 1743-422X [Electronic] England
• PMID: 29587780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Dengue Vaccines

Topics

• Animals
• Antibodies, Neutralizing (blood, immunology)
• Antibodies, Viral (blood, immunology)
• Antibody Specificity (immunology)
• Callithrix (immunology, virology)
• Coinfection (blood, immunology)
• Cross Reactions (immunology)
• Dengue (blood, immunology, prevention & control)
• Dengue Vaccines (immunology)
• Dengue Virus (classification, genetics, immunology)
• Disease Models, Animal
• Genotype
• Neutralization Tests
• Serogroup