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

et al. 2021

Viruses

Self Cite

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 naïve 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.

Section: Discussionsupporting

confidence: 90%

“…Additional isotype-specific depletion experiments are needed to determine the role of these antibodies in SARS-CoV-2 neutralization. Using previous experience from our group [ 28 , 38 ], those experiments are underway using a larger number of well characterized individuals.…”

Section: Discussionmentioning

confidence: 99%

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

Sariol

Pantoja

et al. 2021

Viruses

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“…Another critical aspect to be considered is the timing between the natural infection and a potential vaccination against COVID-19. As others, we highlighted the relevance of the time lapse between infections or immunizations to induce an optimal immune response (29,31,32). Taking in to account the results presented here and those from previous works (16,19,33), and considering the limited vaccine availability worldwide, the vaccination of people with previous history of confirmed COVID-19 may be scheduled to receive as a single shot and deferred to the final phases of the vaccination campaigns and/or to be executed not before than 6 months after the documented infection.…”

Section: Discussionmentioning

confidence: 59%

“…Additional isotypes-specific depletion experiments are needed to determine the specific role of these antibodies in SARS-CoV-2 neutralization. Using previous experience from our group (29,30) those experiments are underway using a larger number of well characterized individuals.…”

Section: Discussionmentioning

confidence: 99%

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

Sariol

Pantoja²,

et al. 2021

Preprint

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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 (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% 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.

“…Recently, Rouers et al provided a detailed dissection on the balance between protection or harm depending on T cells' phenotype in response to primary or secondary dengue infections 28 . Previously, our group determined that cross-protection is associated with the interval of time between DENV and ZIKV infections and mediated by cellular immune responses, particularly CD4 + T cells 29 . An area of active discussion is their role in the context of primary and secondary avivirus infections where it ranges between being polarized to a T helper 1 cell 30 and aiding B cells in the germinal center (GC) 31 to CD4-restricted HLAs associated with less severe infection outcome, expansion of T follicular cells promoting DENV-speci c antibodies and cytotoxic subpopulations as a result of re-exposures 24,32,33 .…”

Section: Introductionmentioning

confidence: 99%

Infection order outweighs the role of CD4+ T cells in tertiary flavivirus infection

Marzan-Rivera

Cruz

et al. 2022

Preprint

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Dengue (DENV) and Zika (ZIKV) are flaviviruses that co-circulate throughout the tropical and subtropical regions. The link between CD4+ T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tertiary flavivirus infection. We show that CD4+ depletion in DENV-primed animals followed by ZIKV-DENV resulted in delayed viremia followed by increased viral replication in tertiary infections and dysregulated adaptive immune responses compared to ZIKV-primed animals followed by DENV-DENV infections. We show a delay in DENV-specific IgM/IgG antibody titers and neutralization in the DENV-primed CD4-depleted animals but not in ZIKV-primed CD4-depleted animals. This study confirms the critical role of CD4+ cells in viremia control and priming of early and robust neutralizing antibody responses during sequential flavivirus infections. Our results also revealed differential cytokine profiles for both infection sequences regardless of CD4+ status. Our work here suggests that the order of flavivirus exposure affects the outcome of a tertiary infection. Our findings have implications for understanding complex immune responses induced by flaviviruses that co-circulate and develop effective flavivirus vaccines.