The serum level of RBD-binding antibodies correlates with SARS-CoV-2 neutralization and can be used for population-level surveillance.

Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKV-specific CD8+ T cells are characterized by a polyfunctional IFN-γ signature with upregulation of TNF-α, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection.

Trypanosoma cruzi infection is characterized by chronic parasitism of non-lymphoid tissues and is rarely eliminated despite potent adaptive immune responses. This failure to cure has frequently been attributed to a loss or impairment of anti-T. cruzi T cell responses over time, analogous to the T cell dysfunction described for other persistent infections. In this study, we have evaluated the role of CD8⁺ T cells during chronic T. cruzi infection (>100 dpi), with a focus on sites of pathogen persistence. Consistent with repetitive antigen exposure during chronic infection, parasite-specific CD8⁺ T cells from multiple organs expressed high levels of KLRG1, but exhibit a preferential accumulation of CD69⁺ cells in skeletal muscle, indicating recent antigen encounter in a niche for T. cruzi persistence. A significant proportion of CD8⁺ T cells in the muscle also produced IFNγ, TNFα and granzyme B in situ, an indication of their detection of and functional response to T. cruzi in vivo. CD8⁺ T cell function was crucial for the control of parasite burden during chronic infection as exacerbation of parasite load was observed upon depletion of this population. Attempts to improve T cell function by blocking PD-1 or IL-10, potential negative regulators of T cells, failed to increase IFNγ and TNFα production or to enhance T. cruzi clearance. These results highlight the capacity of the CD8⁺ T cell population to retain essential in vivo function despite chronic antigen stimulation and support a model in which CD8⁺ T cell dysfunction plays a negligible role in the ability of Trypanosoma cruzi to persist in mice. The parasite Trypanosoma cruzi establishes lifelong infections in humans and other mammals, leading to severe cardiac and gastrointestinal complications known as Chagas disease. Although the factors that enable T. cruzi persistence remain undefined, in this and many other infection models, pathogen persistence has been attributed to the exhaustion of the immune system, particularly of CD8⁺ T cells. Here, we show that the inability of hosts to fully resolve T. cruzi infection is not a result of immune exhaustion and that in fact the T. cruzi-specific CD8⁺ T cell population remains highly competent and actively suppresses parasite outgrowth throughout the chronic infection. These results demonstrate that compromised immunity is not the eventual outcome of all chronic infections and suggest that T. cruzi, and perhaps other pathogens, may employ alternative strategies to subvert immune clearance in the presence of highly functional pathogen-specific effectors. These findings also suggest that interventions to inhibit immune regulatory pathways or to otherwise boost existing immune responses in such infections, will have limited benefit.

Trypanosoma cruziinfects millions of people in Latin America and often leads to the development of Chagas disease.T. cruziinfection can be acquired at or near the bite site of the triatomine vector, butper osinfection is also a well-documented mode of transmission, as evidenced by recent microepidemics of acute Chagas disease attributed to the consumption of parasite-contaminated foods and liquids. It would also be convenient to deliver vaccines forT. cruziby the oral route, particularly live parasite vaccines intended for the immunization of reservoir hosts. For these reasons, we were interested in better understanding immunity toT. cruzifollowing oral infection or oral vaccination, knowing that the route of infection and site of antigen encounter can have substantial effects on the ensuing immune response. Here, we show that the route of infection does not alter the ability ofT. cruzito establish infection in muscle tissue nor does it impair the generation of a robust CD8⁺T cell response. Importantly, oral vaccination with attenuated parasites provides protection against wild-type (WT)T. cruzichallenge. These results strongly support the development of whole-organism-based vaccines targeting reservoir species as a means to alleviate the burden of Chagas disease in affected regions.

Human norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by the FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set of fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2-/-) express a limited array of HBGAs. Thus, nonsecretors have less diverse norovirus strain infections, including resistance to the epidemiologically dominant GII.4 strains. Because future human norovirus vaccines will comprise GII.4 antigen and because secretor phenotype impacts GII.4 infection and immunity, nonsecretors may mimic young children immunologically in response to GII.4 vaccination, providing a needed model to study cross-protection in the context of limited pre-exposure. By using specimens collected from the first characterized nonsecretor cohort naturally infected with GII.2 human norovirus, we evaluated the breadth of serologic immunity by surrogate neutralization assays, and cellular activation and cytokine production by flow cytometry. GII.2 infection resulted in broad antibody and cellular immunity activation that persisted for at least 30 days for T cells, monocytes, and dendritic cells, and for 180 days for blocking antibody. Multiple cellular lineages expressing interferon-γ and tumor necrosis factor-α dominated the response. Both T-cell and B-cell responses were cross-reactive with other GII strains, but not GI strains. To promote entry mechanisms, inclusion of bile acids was essential for GII.2 binding to nonsecretor HBGAs. These data support development of within-genogroup, cross-reactive antibody and T-cell immunity, key outcomes that may provide the foundation for eliciting broad immune responses after GII.4 vaccination in individuals with limited GII.4 immunity, including young children.

While death due to Zika virus (ZIKV) infection has been described, reports of fatal cases have been infrequent and no systematic reviews on the subject have been published. A systematic review of the literature in four databases was performed to assess fatal outcomes of postnatal ZIKV infection and the available evidence that links ZIKV infection to death. Three hundred and eleven articles were retrieved; 20 of them were epidemiological reports from surveillance agencies and ministries of health. After screening by abstract and title, 59 articles were selected for full-text assessment. Of these, 35 were excluded (with reasons) and 24 were finally included for qualitative analysis. A total of 51 reported deaths associated with ZIKV infection in nine countries were identified. The majority of cases (56.9%) were not related to Guillain-Barré syndrome. Cases from three countries accounted for 67.6% of the deaths. ZIKV infection was laboratory-confirmed in the majority of cases (64.7%). ZIKV was not considered to be a dangerous, and much less a lethal pathogen, until very recently. However, an increasing number of fatalities have been published in the literature since the first death was reported in 2016. Additional research is needed to elucidate factors that may mediate the pathogenesis of severe, atypical, and fatal disease.