Repeated exposure to dengue virus elicits robust cross neutralizing antibodies against Zika virus in residents of Northeastern Thailand

Sararat Hattakam,Sujan Shresta,Montarop Yamabhai,Melanie McCauley,Annie Elong Ngono

doi:10.1038/s41598-021-88933-x

Abstract

Zika virus (ZIKV) and dengue virus (DENV) are antigenically related mosquito-borne flaviviruses. ZIKV is becoming increasingly prevalent in DENV-endemic regions, raising the possibility that pre-existing immunity to one virus could modulate the response to a heterologous virus, although whether this would be beneficial or detrimental is unclear. Here, we analyzed sera from residents of a DENV-endemic region of Thailand to determine the prevalence of DENV-elicited antibodies capable of cross-neutralizing ZIKV. Sixty-one participants who were asymptomatic and unselected for viral serostatus were enrolled. Among them, 52 and 51 were seropositive for IgG antibody against DENV or ZIKV E proteins (ELISA assay), respectively. Notably, 44.23% (23/52) of DENV seropositive participants had serological evidence of multiple exposures to DENV, and these subjects had strikingly higher titers and broader reactivities of neutralizing antibodies (NAbs) against ZIKV and DENV heterotypes compared with participants with serological evidence of a single DENV infection (25/52, 48.1%). In total, 17 of the 61 participants (27.9%) had NAbs against ZIKV and all four DENV serotypes, and an additional 9 (14.8%) had NAbs against ZIKV and DENV1, 2, and 3. NAbs against DENV2 were the most prevalent (44/61, 72.1%) followed by DENV3 (38/61, 62.3%) and DENV1 (36/61, 59.0%). Of note, anti-ZIKV NAbs were more prevalent than anti-DENV4 NAbs (27/61, 44.3% and 21/61, 34.4%, respectively). Primary ZIKV infection was detected in two participants, confirming that ZIKV co-circulates in this region. Thus, residents of DENV-endemic regions with repeated exposure to DENV have higher titers of NAbs against ZIKV than individuals with only a single DENV exposure.

Highlights

Most dengue virus (DENV) and Zika virus (ZIKV) infections are asymptomatic, both viruses can have devastating and potentially life-threatening consequences
Cross-reactive monoclonal Abs generated against ZIKV mediate DENV ADE22, inactivated ZIKV vaccination enhances DENV disease severity[23], and we showed that maternally acquired ZIKV Abs cause severe dengue-like d isease[24]
Blood samples were collected from these individuals between April and July 2016, at which time ZIKV had been documented in the region for more than a d ecade[2]

Summary

Introduction

Most DENV and ZIKV infections are asymptomatic, both viruses can have devastating and potentially life-threatening consequences. ZIKV infections in adults may be associated with Guillain–Barré syndrome[6], and infections in pregnant women can lead to severe congenital malformations, such as microcephaly, in the offspring[7]. These potential outcomes, together with the rapid regional spread of ZIKV, led the World Health Organization to declare ZIKV a public health emergency in February 2 0168. In vitro studies with cultured animal and human cells suggest that ZIKV-cross-reactive DENV-elicited antibodies (Abs) can mediate Ab-dependent enhancement (ADE) of infection, providing a mechanism by which exposure to DENV might increase the severity of a subsequent ZIKV infection[16–21]. We found a striking association between repeated DENV infection and the presence of a strong and broad cross-neutralizing Ab (cross-NAb) response to ZIKV and DENV heterotypes

Methods

Results

Conclusion