Can Zika virus antibodies cross-protect against dengue virus?
Authors: Kevin K Ariën, Johan Michiels, Nikki Foqué, Leo Heyndrickx, Marjan Van Esbroeck
Journal: The Lancet Global Health (2018)

Guilherme Ribeiro and colleagues (February, 2018)1Ribeiro GS Kikuti M Tauro LB et al.Does immunity after Zika virus infection cross-protect against dengue?.Lancet Glob Health. 2018; 6: e140-e141Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar report a major downward trend in dengue virus infection cases after the recent Zika virus outbreak in the Americas. They used epidemiological data collected between 2009 and 2017 in Salvador, Brazil, to suggest that the decline in dengue virus infection cases observed since 2015 could be the result of cross-protective immunity to dengue virus induced by Zika virus infection. As part of the National Reference Centre for Arboviruses, we do neutralisation assays for a variety of arboviruses, including Zika and dengue viruses.2De Smet B Van den Bossche D van de Werve C et al.Confirmed Zika virus infection in a Belgian traveler returning from Guatemala, and the diagnostic challenges of imported cases into Europe.J Clin Virol. 2016; 80: 8-11Crossref PubMed Scopus (19) Google Scholar Between 2016 and 2017, we examined 382 human serum samples (from 323 patients) for Zika virus neutralising antibodies. A subset of 55 serum samples (from 44 patients) were examined for in-vitro neutralising potential against both Zika virus and dengue virus serotypes 1–4. Samples with low Zika virus neutralisation titres (unlikely to be Zika) and high dengue virus neutralisation titres (likely to be dengue) were removed from the subset before further analysis. In a serum sample with pre-existing dengue virus neutralising antibodies, measuring the specific contribution of Zika virus antibodies to the neutralisation of dengue virus is difficult (if not impossible). Therefore, we limited our analysis to dengue virus-naive patients with a documented Zika virus infection (confirmed by PCR or virus neutralisation; n=21) and investigated dengue virus neutralisation potential in vitro. Only one of 21 Zika virus serum samples showed a weak cross-neutralisation titre (the neutralisation titre that inhibited 90% of viral infection [NT90] was 86) against dengue virus serotype 2, and two additional serum samples showed NT50≥50. This finding is in line with earlier reports that showed the absence of Zika virus neutralisation among primary dengue virus infections and low-frequency cross-neutralisation in repeat dengue virus infections,3Collins MH McGowan E Jadi R et al.Lack of durable cross-neutralizing antibodies against Zika virus from dengue virus infection.Emerg Infect Dis. 2017; 23: 773-781Crossref PubMed Scopus (102) Google Scholar, 4Swanstrom JA Plante JA Plante KS et al.Dengue virus envelope dimer epitope monoclonal antibodies isolated from dengue patients are protective against Zika virus.MBio. 2016; 7: e01123-e01216Crossref PubMed Scopus (161) Google Scholar suggesting that independent neutralising antibody populations against these two viruses are raised. This picture is more complex in a population with pre-existing flavivirus immunity resulting from previous exposures to flaviviruses other than Zika or vaccination, as is the case in Latin America, and the attribution of immunity against Zika virus to dengue infection in such a population can only be determined when pre-Zika infection archived serum samples are available. Of note, the epidemiological data presented by Ribeiro and colleagues1Ribeiro GS Kikuti M Tauro LB et al.Does immunity after Zika virus infection cross-protect against dengue?.Lancet Glob Health. 2018; 6: e140-e141Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar already showed a downward trend in dengue virus infection cases in 2012 and 2013, before the Zika virus epidemic occurred. The further decline in dengue virus infections in 2016 and 2017 could merely result from existing immunity against dengue virus in the population of Salvador, and not necessarily from Zika virus antibodies that cross-protect against subsequent dengue virus infections. We declare no competing interests. The National Reference Centre for Arboviruses is partially supported by the Belgian Ministry of Social Affairs through a fund within the Health Insurance System. The Institute of Tropical Medicine is a member of the ZikaPLAN consortium that received funding from the European Union's Horizon 2020 research and innovation programme under ZikaPLAN (grant agreement 734584). Does immunity after Zika virus infection cross-protect against dengue?Zika and dengue viruses are closely related flaviviruses, with immunological interactions and identical urban, mosquito-borne transmission.1 Therefore, the recent introduction of Zika virus into the Americas and large-scale exposure of a uniformly previously unexposed population could affect subsequent transmission of dengue virus. This hypothesis had been untested, largely because sufficient epidemiological data were not available from affected locations. We explored this hypothesis in Salvador, the fourth largest city in Brazil (population 2·9 million), where extensive transmission of dengue viruses 1–42,3 occurred before the introduction and spread of Zika virus in 2015. Full-Text PDF Open AccessCan Zika virus antibodies cross-protect against dengue virus? – Authors' replyWe welcome the comments by Kevin Ariën and colleagues on our recent Correspondence, in which we presented epidemiological data showing a large decline in detected dengue virus infection cases in Salvador, Brazil, following the 2015 Zika virus outbreak.1 Our aim was to raise the hypothesis that massive population exposure to Zika virus might have an inhibitory role in dengue virus transmission and symptomatic infections, and to open a new avenue for discussion, experimental studies, and epidemiological data analyses from other groups. Full-Text PDF Open Access