Dengue virus neutralizing antibody: a review of targets, cross-reactivity, and antibody-dependent enhancement

Abstract

Dengue is the most common viral infection spread by mosquitoes, prevalent in tropical countries. The acute dengue virus (DENV) infection is a benign and primarily febrile illness. However, secondary infection with alternative serotypes can worsen the condition, leading to severe and potentially fatal dengue. The antibody raised by the vaccine or the primary infections are frequently cross-reactive; however, weakly neutralizing, and during subsequent infection, they may increase the odds of antibody-dependent enhancement (ADE). Despite that, many neutralizing antibodies have been identified against the DENV, which are thought to be useful in reducing dengue severity. Indeed, an antibody must be free from ADE for therapeutic application, as it is pretty common in dengue infection and escalates disease severity. Therefore, this review has described the critical characteristics of DENV and the potential immune targets in general. The primary emphasis is given to the envelope protein of DENV, where potential epitopes targeted for generating serotype-specific and cross-reactive antibodies have critically been described. In addition, a novel class of highly neutralizing antibodies targeted to the quaternary structure, similar to viral particles, has also been described. Lastly, we have discussed different aspects of the pathogenesis and ADE, which would provide significant insights into developing safe and effective antibody therapeutics and equivalent protein subunit vaccines.

Serological immune biomarker for disease severity in dengue‐infected pediatric hospitalized patients

“…However, recent studies show that these immature viruses could be taken up by prM antibodies rendering them susceptible to ADE. [21][22][23] Numerous studies have focused on identifying biological parameters in clinical samples that differ between severe and nonsevere cases. [24][25][26] PRNT is considered the "Gold standard" method for testing neutralization potential of antibodies.…”

Antibody-Dependent Enhancement with a Focus on SARS-CoV-2 and Anti-Glycan Antibodies

“…As summarized in several reviews (e.g., [ 1 , 6 , 21 , 22 ]), the ADE researchers consider that ADE-associated antibodies are AEAbs, i.e., the antibodies which had emerged in response to previous infection and are still present by the time of a new infection. However, a homologous or heterologous viral genotype causes a new generation of virus-specific antibodies, the role of which in ADE is difficult to determine for several reasons.…”

Immunoinformatic approach to design CTL epitope based chimeric vaccine targeting multiple serotypes of dengue virus

“…The immunity against cross-serotype infections in an average young adult is only partial and temporary. Partial immunity acts as a catalyst for disease severity (Sarker et al, 2023). An estimated 3.9 billion people are at risk of infection, of which 96 million people manifest clinically with severe complications such as dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS) (Bhatt et al, 2013).…”