High frequency of pre-existing neutralizing antibody responses in patients with dengue during an outbreak in Central Brazil

Angela Ferreira Lopes de Teive e Argolo, Valéria Christina de Rezende Féres, Marli Tenório Cordeiro, Lucimeire Antonelli da Silveira, Adriana Oliveira Guilarde, Ernesto Torres de Azevedo Marques, Wayner Vieira de Souza, Celina Maria Turchi Martelli

This study aims to identify dengue neutralizing antibody response in patients with dengue from a well-characterized cohort during an outbreak in central Brazil, 2012-2013. We analyzed paired samples from 40 patients with severe dengue and 20 patients with dengue. Eligibility criteria were: IgM, NS1Ag and/or RT-PCR positivity and positive IgG result. Plaque reduction neutralization test (PRNT50) from DENV-1 to DENV-4 was performed to identify serotype-specific NAbs response. An infecting serotype was defined as ≥4-fold increase in DENV NAbs in paired samples. Monotypic response was classified as PRNT50 ≥ 1/20 to only one DENV serotype, and multitypic response was considered to be PRNT50 ≥ 1/20 to two or more serotypes simultaneously. Patients were mainly adults. Virological dengue infection was confirmed by RT-PCR: DENV-4(n = 14) and DENV-1(n = 10). Forty-four out of 60(73.3 %) patients had NAbs to DENV-4, DENV-1(68.3 %), DENV-2(68.3 %) and DENV-3(61.6 %) respectively. Fifteen percent of the cases presented monotypic response, whereas 85 % had multitypic response. DENV-4 infected-patients presented the greatest difference in PRNT50 titers compared with other serotypes. Pre-existing DENV NAbs was not correlated with disease severity. This was the first time that DENV-4 was implicated in an epidemic in the region. Our data indicates high exposure of multiple DENV serotypes in all age groups in the pre-dengue vaccine era and also previous to Zika virus introduction in Brazil.