CHIKV-ZIKV antibody Co-positivity and preserved neutralising activity in a Nigerian arboviral study

Arboviral coinfections complicate public health responses in endemic regions. Antibody-dependent enhancement (ADE) is a well-characterised phenomenon among related flaviviruses, yet its relevance to cross-family alphavirus and flavivirus interactions remains unclear. We examined patterns of CHIKV-ZIKV coinfection in a Nigerian cohort and asked whether the serological data were consistent with antibody-mediated or alternative mechanisms.

We carried out serological surveillance of 871 participants across three ecological zones in Nigeria, measuring IgG and IgM responses to chikungunya virus (CHIKV), Zika virus (ZIKV) and dengue virus (DENV) by immunoblot. Dengue virus was tested as part of the same three-virus panel, and CHIKV-DENV and DENV-ZIKV co-positivity results are reported alongside the primary CHIKV-ZIKV analysis. Functional antibody activity was assessed by plaque reduction neutralisation test (PRNT) in a subset of 150 sera. Observed-to-expected (O/E) co-positivity ratios were calculated under an assumption of immunological independence. Complementary computational analyses of viral envelope proteins were performed to flag molecular features that might inform future mechanistic work.

CHIKV-ZIKV IgG co-seropositivity was more frequent than expected under independence, with 151 observed co-positive samples against 108.33 expected (O/E = 1.39). Recent CHIKV-ZIKV IgM co-positivity showed a larger but numerically sparse enrichment, with 6 observed against 2.44 expected (O/E = 2.46), that is, roughly 2.5-fold more frequent than expected under immunological independence. Because subgroup overlap counts were not fully available in the aggregate tables, a bounded sensitivity analysis was performed. Across all allocations consistent with the reported marginals and the overall IgG overlap, the possible O/E range was 1.77 to 2.30 in HIV-positive participants and 0.89 to 1.07 in HIV-negative participants. For recruitment stream, the possible O/E ranges were 0.93 to 1.21 in blood donors and 1.34 to 1.61 in outpatients. PRNT showed preserved neutralising activity among the tested sera: CHIKV neutralisation in 76/97 (78.4%) CHIKV IgG-positive sera and ZIKV neutralisation in 20/29 (69.0%) ZIKV IgG-positive sera. Exploratory CD4-stratified analysis was possible only in the PRNT subset with available CD4 values and was descriptive, given very small denominators.

These findings point to CHIKV-ZIKV antibody co-positivity in a heterogeneous Nigerian serosurvey, but the magnitude differs by antibody class and must be read cautiously. IgG co-seropositivity showed a modest excess, whereas the stronger 2.5-fold signal applied to recent IgM co-positivity and rested on only six co-positive samples and should therefore be regarded as exploratory. The PRNT data show preserved neutralising activity in the tested subset; the study does not directly test ADE. The analysis is seroepidemiological and descriptive: it characterises serological co-positivity and neutralisation but does not establish an immunological mechanism or a causal relationship. Exact subgroup and CD4-adjusted analyses should be prioritised should the original row-level dataset become available.