Relative contribution of dengue prM- and E-specific polyclonal antibodies to neutralization and enhancement

Abstract

Summary. -Viral surface proteins, premembrane protein (prM) and envelope (E) protein have been shown to induce a production of antibodies that are involved in both enhancement and neutralization. To explore the feasibility of modifying the relative immune responses to prM and E proteins, four DNA constructs were created and administered into groups of Balb/c mice; pPW01 contains prM and E genes of DENV1, pPW02 contains prM and E genes of DENV2, pPW03 contains DENV1 prM and DENV2 E, and pPW04 contains DENV2 prM and DENV1 E. Exchange of either prM or E from a heterologous serotype does not appear to have an effect on the immunogenicity of the proteins. We have proved that the chimeric pPW03 and pPW04 constructs can produce humoral response in mice. Immunized sera were subjected to neutralization and enhancement assays against DENV2. The results showed that only serotype-specific anti-E antibodies conferred protective function, while the cross-reactive anti-E and anti-prM enhanced infection. In addition, the enhancement of DENV2 infection exhibited a serotype-preference for anti-E antibodies while such response was not observed with antiprM, reflecting a degree of structural conservation of prM. Taken together, neutralization and enhancement appeared to occur at the same time during the course of infection. Successful prevention of severe symptoms of DENV infection depends on the ability to induce high levels of neutralizing antibodies to subdue the effect of enhancing antibodies.

Antibody‐dependent enhancement (ADE) of dengue virus: Identification of the key amino acid that is vital in DENV vaccine research

“…31,32 Therefore, ways of reducing the occurrence of ADE must be considered when developing vaccines. Because anti-prM antibodies could enhance DENV infection, 33,34 and the epitopes of these infection-enhancing anti-prM antibodies are mainly located in the amino acid residues of the pr peptide, 24,26 strategies at the molecular level can be developed to replace the ADE epitope, thus reducing ADE. This may eventually provide new insights and novel ideas for vaccine development.…”

Vaccines Against Dengue and West Nile Viruses in India: The Need of the Hour

“…Although these are closely related with only minor difference in genetic and proteins, NAb response against one serotype does not protect against another (46,75). Antibody-dependent enhancement (ADE) of infection is an immunopathological phenomenon, whereby monocytes or macrophages take up infectious immune complexes and are infected at a higher rate (49,50), with the potential to result in DHF (92,93,114). This is mostly specific to DEN infection, through Fcc receptor-mediated uptake of immune complexes.…”

NS1: a promising novel target antigen with strong immunogenicity and protective efficacy for avian flavivirus vaccine development

“…However, it is critical to consider that cross-reactive antibodies, while poorly neutralizing, can lead to antibody-dependent enhancement ( ADE ) following flavivirus infection and vaccination. For instance, a Dengue virus serotype 1 ( DENV-1 ) prM-E DNA vaccine conferred protection against DENV-1 infection but remains ineffective against DENV-2, DENV-3, and DENV-4 ( Rodpothong et al, 2016 ). Paradoxically, it even enhanced the infectivity of the other three serotypes ( Muhammad Azami et al, 2020 ; Rodpothong et al, 2016 ).…”

“…For instance, a Dengue virus serotype 1 ( DENV-1 ) prM-E DNA vaccine conferred protection against DENV-1 infection but remains ineffective against DENV-2, DENV-3, and DENV-4 ( Rodpothong et al, 2016 ). Paradoxically, it even enhanced the infectivity of the other three serotypes ( Muhammad Azami et al, 2020 ; Rodpothong et al, 2016 ). Similarly, when mice previously immunized with a DENV quadrivalent vaccine ( DENVax ) were infected with Zika virus ( ZIKV ), the titer and pathogenicity of ZIKV increased in the mice ( Shukla et al, 2020 ).…”