Crisanta Serrano-Collazo

Bio: Crisanta Serrano-Collazo is an academic researcher from University of Puerto Rico, Medical Sciences Campus. The author has contributed to research in topics: Dengue virus & Zika virus. The author has an hindex of 3, co-authored 9 publications receiving 41 citations.

Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Abstract: Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. Here we show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. We show that previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV. The time interval between ZIKV and subsequent DENV infection further affects the immune response. A mid-convalescent period of 10 months after ZIKV infection results in higher and more durable antibody and T cell responses to DENV infection than a short period of 2 months. In contrast, previous ZIKV infection does not affect DENV viremia or pro-inflammatory status. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.

Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination.

Abstract: Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naive subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.

Effective control of early Zika virus replication by Dengue immunity is associated to the length of time between the 2 infections but not mediated by antibodies.

Abstract: Little is known about the contribution of virus-specific and cross-reacting antibodies (Abs) or the cellular immune response generated by a primary dengue (DENV) infection on the course of a secondary zika (ZIKV) infection in vivo. Here we show that the length of time between DENV/ZIKV infections has a qualitative impact on controlling early ZIKV replication. Depletion of DENV2-specific Abs in sera confirmed that those type-specific Abs do not contribute to ZIKV control. We show that the magnitude and durability of the neutralizing antibodies (nAbs) induced by a secondary ZIKV infection is modest compared to the response induced after a secondary heterologous DENV infection. Our in vivo results are showing a complex interplay between the cellular and innate immune responses characterized by a high frequency of plasmacytoid dendritic cells (pDC) correlating with an increase in the frequency of DENV antigen specific T cells and a significant control of ZIKV replication which is time dependent. Taken together, our results suggest that early after ZIKV infection other mechanisms such as the innate and cellular immune responses may play a predominant role in controlling ZIKV replication. Regardless of the time elapsed between infections there was no evidence of in vivo antibody-dependent enhancement (ADE) of ZIKV by DENV immunity. These findings have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs and schedules among others.

Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

Abstract: On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2 We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (6271%), followed by IgG4 (1525%), IgG3 (1356%), and IgG2 (847%) during the tested period The IgA was detectable in 2881% of subjects Only 6271% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2 One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection

Time elapsed between Zika and dengue virus infections affects antibody and T cell responses

Abstract: The role of Zika virus (ZIKV) immunity on subsequent dengue virus (DENV) infections is relevant to anticipate the dynamics of forthcoming DENV epidemics in areas with previous ZIKV exposure. We study the effect of ZIKV infection with various strains on subsequent DENV immune response after 10 and 2 months of ZIKV infection in rhesus macaques. Our results show that a subsequent DENV infection in animals with early- and middle-convalescent periods to ZIKV do not promote an increase in DENV viremia nor pro-inflammatory status. Previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV, and different time intervals between infections alter the magnitude and durability of such responses—more after longer ZIKV pre-exposure. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.

Zika virus infection enhances future risk of severe dengue disease

Abstract: The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naive. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil.

Abstract: The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

Vector Competence: What Has Zika Virus Taught Us?

Abstract: The unprecedented outbreak of Zika virus (ZIKV) infection in the Americas from 2015 to 2017 prompted the publication of a large body of vector competence data in a relatively short period of time. Although differences in vector competence as a result of disparities in mosquito populations and viral strains are to be expected, the limited competence of many populations of the urban mosquito vector, Aedes aegypti, from the Americas (when its susceptibility is viewed relative to other circulating/reemerging mosquito-borne viruses such as dengue (DENV), yellow fever (YFV), and chikungunya viruses (CHIKV)) has proven a paradox for the field. This has been further complicated by the lack of standardization in the methodologies utilized in laboratory vector competence experiments, precluding meta-analyses of this large data set. As the calls for the standardization of such studies continue to grow in number, it is critical to examine the elements of vector competence experimental design. Herein, we review the various techniques and considerations intrinsic to vector competence studies, with respect to contemporary findings for ZIKV, as well as historical findings for other arboviruses, and discuss potential avenues of standardization going forward.