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Objectives: The dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on breakthrough infections during follow-up. Methods: Spike-specific MBC and T cells were quantified at inclusion and after two doses of mRNA vaccine in a longitudinal cohort of 85 naive and 64 recovered participants (47 with positive serology and 17 with negative serology after infection). Results: At inclusion, there was minimal spike-specific MBC in naive SARS-CoV-2 individuals. After the second vaccine dose, MBCs were significantly boosted in naive individuals, but reached a significantly lower level than that observed even in unvaccinated SARS-CoV-2 convalescents (p<0.001). Furthermore, while the secondary memory B cell (MBC) population consisted of 100%, 33%, and 76% IgG+, IgM+, and IgA+ expressing cells, respectively, in the unexposed group, the MBC response showed a significant decrease across all isotypes. Similarly, although secondary specific IgG+, IgM+, and IgA+-MBC isotypes were found in 100%, 39%, and 76% of the unexposed participants, respectively, the magnitude of the MBC levels was significantly lower for all the isotypes compared to convalescents. Interestingly, convalescents without an initial serological response had a lower MBC response, like what found in unexposed subjects. There was an inverse correlation between specific MBCs (r=-0.307; p=0.027), especially for isotype IgA+ (r=-0.279, p=0.045), and the time since the second vaccination dose. Furthermore, during a median follow-up of 434 days (IQR, 339-495), 49 out of 149 individuals (33%) became infected, 29 in naive and 20 in convalescent individuals, showing a significant correlation between spike-specific MBC magnitude after vaccination and the time for SARS-CoV-2 infection, especially for IgA+/IgG+ MBC isotypes. Conclusions: MBCs were primed by mRNA-based vaccination in most cases, but SARS-CoV-2 naive individuals had a blunted specific MBC response, and this was associated with a shorter time to breakthrough SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with cancer are at increased risk of serious COVID-19, thus, vaccination is especially relevant for this population. However, lower responses are expected, secondary to immunosuppression. Several studies have been conducted to determine how cancer patients respond to vaccination, but these studies include heterogenous groups of patients who received different types of treatment and had a variety of comorbidities that may influence COVID-19 susceptibility. This study aimed to determine the vaccination response in a specific subgroup of breast cancer patients receiving treatment with CDK4/6 inhibitors. Our study shows that SARS-CoV-2 vaccines are safe and effective in terms of humoral response in these patients, achieving antibody titers even higher than healthy controls. Surprisingly, the patients show an impaired cellular immune response, which could entail shorter protection. This finding should be considered for vaccination strategies. Few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). We conducted a prospective, single-center study of patients with breast cancer treated with CDK4/6i who received mRNA-1273 vaccination, as well as a comparative group of healthcare workers. The primary endpoint was to compare the rate and magnitude of humoral and T-cell response after full vaccination. A better neutralizing antibody and anti-S IgG level was observed after vaccination in the subgroup of women receiving CDK4/6i, but a trend toward a reduced CD4 and CD8 T-cell response in the CDK4/6i group was not statistically significant. There were no differences in the rate of COVID-19 after vaccination (19% vs. 12%), but breakthrough infections were observed in those with lower levels of anti-S IgG and neutralizing antibodies after the first dose. A lower rate of CD4 T-cell response was also found in those individuals with breakthrough infections, although a non-significant and similar level of CD8 T-cell response was also observed, regardless of breakthrough infections. The rate of adverse events was higher in patients treated with CDK4/6i, without serious adverse events. In conclusion, there was a robust humoral response, but a blunted T-cell response to mRNA vaccine in women receiving CDK4/6i, suggesting a reduced trend of the adaptative immune response. [ABSTRACT FROM AUTHOR]

Objective: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells (MBCs) after the SARS-CoV-2 mRNA-based vaccination and its impact on incident SARS-CoV-2 infections. Methods: This was a longitudinal study of 149 healthcare workers (HCWs) that included 85 unexposed individuals that were subdivided according to previous T-cell cross-reactivity, who were compared to 64 convalescent HCWs. Changes in specific T-cell response and memory B-cell (MBC) levels were compared at baseline and after two doses of the SARS-CoV-2 mRNA-based vaccine. Results: A cross-reactive T-cell response was found in 59% of unexposed individuals before vaccination. Antibodies against HKU1 positively correlated with OC43 and 229E antibodies. Spike-specific MBCs was scarce in unexposed HCWs regardless of the presence of baseline T-cell cross-reactivity. After vaccination, 92% and 96% of unexposed HCWs with cross-reactive T-cells had CD4+ and CD8+ T-cell responses to the spike protein, respectively. Similar results to that were found in convalescents (83% and 92%, respectively). Contrarily, higher than that which was observed in unexposed individuals without T-cell cross-reactivity showed lower CD4+ and CD8+ T-cell responses (73% in both cases, p = 0.03). Nevertheless, previous cross-reactive T-cell response was not associated with higher levels of MBCs after vaccination in unexposed HCWs. During a follow-up of 434 days (IQR, 339–495) after vaccination, 49 HCWs (33%) became infected, with a significant positive correlation between spike-specific MBC levels and isotypes IgG+ and IgA+ after vaccination and a longer time to get infected. Interestingly, T-cell cross-reactivity did not reduce the time to vaccine breakthrough infections. Conclusion: While pre-existing T-cell cross-reactivity enhances the T-cell response after vaccination, it does not increase SARS-CoV-2-specific MBC levels in the absence of previous infection. Overall, the level of specific MBCs determines the time to breakthrough infections, regardless of the presence of T-cell cross-reactivity. [ABSTRACT FROM AUTHOR]

The Japón, Tailandia and China Sur deposits in the Pelusa mineralized area correspond to a hematite‐dominant IOCG clan within the coastal Cordillera in the Antofagasta Region, Northern Chile, and their mineralization occurs in basaltic to andesitic volcanic rocks of the Jurassic La Negra Formation. In addition to geological and mineralogical descriptions, bulk chemistry of the host rocks, microthermometric and sulfur isotropic analyses were performed to elucidate ore‐forming characteristics of the three orebodies. Chemical data of the host rocks indicate a subalkaline calc‐alkaline affinity with enrichment of the incompatible LILEs, displaying a typical pattern of igneous rocks formed in subduction zones as a general characteristic of the Jurassic‐Lower Cretaceous magmatic arc. Chalcopyrite is the predominant hypogene copper mineral, that variously occurs as veinlets, disseminations and breccia matrix. Fluid inclusions data indicate formation temperatures of the hypogene mineralization ranging mostly from 186 to 377°C, with a high‐salinity range of 30.1 and 45.0 wt% NaCl. The sulfur isotopic ratios (δ34SCDT) of pyrite and chalcopyrite present a narrow range of values from −10.6 to −7.5‰. The negative values in the limited range imply that sulfide minerals of the Pelusa area were formed under a relatively oxidizing and/or neutral pH condition, compared with other Chilean IOCG deposits. [ABSTRACT FROM AUTHOR]

Despite in vitro activity of interferon-β (IFN-β) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-β treatment in a cohort of 3590 patients hospitalized with COVID-19 during March–April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-β. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-β for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82–1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-β therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-β was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-β was not associated with a higher rate of ICU admission or mortality. [ABSTRACT FROM AUTHOR]

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the impact of SARS-COV-2-specific memory B cells (MBC) on the immune response after two doses of mRNA-based Comirnaty COVID-19 vaccine in seronegative health care workers. This study is seeking a rationale for boosting vaccines. Methods: Longitudinal study including 31 seronegative health care workers with undetectable specific MBCs (IgG−MBC− group), 24 seronegative with detectable specific MBCs (IgG−MBC+ group), and 24 seropositive with detectable specific MBCs (IgG+MBC+ group). The level of antibodies that inhibit ACE2-RBD interaction, and anti-Spike IgG, IgA, and IgM antibodies was quantified by ELISA. In addition, specific memory B and T cells were quantified by flow cytometry. Results: The level of specific MBCs, and isotypes, in the IgG−MBC− group was lower compared to that found in IgG−MBC+ (p = 0.0001) and IgG+MBC+ (p < 0.0001) groups, respectively. ACE2-RBD neutralizing antibodies and anti-S IgG antibodies were at lower levels in the IgG−MBC−group after the vaccine. Specific MBCs directly correlated with specific CD4+ T cells (although not significant, p = 0.065), while no correlation was found with specific CD8+ T cells (p = 0.156) after the vaccine. In parallel, ACE2-RBD neutralizing antibodies only positively correlated with specific CD4+ T cells (p = 0.034). Conclusion: IgG−MBC− individuals showed the worst humoral and cellular responses, both in frequency and magnitude, after vaccination. Individuals whose antibodies wane and become undetectable after a given period of time post vaccination and show no specific MBCs are less protected and hence are good candidates for boosting vaccine. On the other hand, seronegative individuals with specific MBC showed faster and higher responses compared to the IgG−MBC− group. [ABSTRACT FROM AUTHOR]

The risk of reinfection could be related to the initial SARS-CoV-2 clinical presentation, but there are no data about the risk change after SARS-CoV-2 vaccination. We evaluated the rate of reinfection in an inception cohort study of 4943 health care workers (HCWs) according to symptoms and serologic results during March–May 2020. Incidence rates (IR) and IR ratios (IRR) before and after SARS-CoV-2 vaccination were determined by adjusting Poisson models. Overall, 1005 HCWs (20.3%) referred COVID-19 suggestive symptoms during the first surge of disease, and 33.5% and 55% presented a positive PCR or serology result, respectively. Meanwhile, 13% of asymptomatic HCWs had specific antibodies. During a follow up of 3422.2 person-years before vaccination, the rate of reinfection among seropositive individuals was 81% lower for those who were symptomatic compared with those who were asymptomatic (IRR of 0.19; 95% CI, 0.05–0.67; p = 0.003). During the 3100 person-years period after vaccination, an overall 74% decrease in the rate of infection was observed (IRR of 0.26; 95% CI, 0.21–0.32; p < 0.001), with a significant 83% and 70% decrease in seropositive and seronegative HCWs, respectively. In conclusion, the risk of SARS-CoV-2 reinfections is closely related to the clinical and serological presentation of COVID-19. COVID-19 vaccination further decreases the risk of reinfection more markedly among seropositive. [ABSTRACT FROM AUTHOR]

The predictive capacity of thymic volume in CD4 T-cell loss after treatment interruption in HIV-infected patients with high nadir CD4 count is analyzed. The thymic volume for the first time predicts CD4 T-cell loss in patients with nadir CD4 count greater than or equal to 250 cells/muL under treatment interruption.

SARS-CoV-2 spike mRNA vaccines have shown remarkable clinical efficacy in the general population, although the nature of T-cell priming is not fully understood. We performed longitudinal spike-, membrane-, and nucleocapsid-specific T-cell analysis in individuals with past infection and infection-naïve individuals with cross-reactivity. We found an additional enhancement of T-cell response to the structural membrane (M) and nucleocapsid (N) SARS-CoV-2 proteins after mRNA vaccine in these individuals. Thus, despite the spike-specific response, we found that the first dose of the vaccine boosted a significant CD8 cell response to M and N proteins, whereas no cellular response to those proteins was found in infection-naïve individuals without pre-existing cross-reactivity who were tested for eventual asymptomatic infection. These findings highlight the additional benefit of mRNA vaccines as broad boosters of cellular responses to different viral epitopes in these individuals and suggest extended protection to other viral variants. [ABSTRACT FROM AUTHOR]

Background: Healthcare workers (HCWs) are at increased risk since they are directly exposed to SARS‐CoV‐2‐infected patients, and nevertheless, some remain without the development of anti‐SARS‐CoV‐2 antibodies or related symptoms, suggesting less susceptibility to the infection. Methods: This cross‐sectional, case‐control study aimed to compare SARS‐CoV‐2 T‐cell response by two different technologies, the analysis of IFN‐γ+ CD8+/CD4+ T cells by flow cytometry and the quantification of IFN‐γ release by ELISA‐related assay (without cell discrimination), both after SARS‐CoV‐2 stimulation among uninfected and convalescent HCWs. Results: A high proportion of uninfected HCWs (53.8%) had pre‐existing IFN‐γ+ CD8 T‐cell response after stimulation with at least one of the structural viral proteins S, M or N, while 35.9% had pre‐existing IFN‐γ+ CD4 T‐cell response. This proportion was nearly or greater than 90% among convalescent HCWs. Interestingly, the magnitude of the response in uninfected was lower compared to that found in convalescent HCWs, using both methods. The concordance, quantifying the specific cellular response in convalescent HCWs, between both methods was 94.1% comparing CD8 T‐cell response and 89.7% comparing CD4 T‐cell response. This concordance was lower but still high in uninfected HCWs (76.5%) comparing CD8 T‐cell response and 71.8% comparing CD4 T‐cell response. Conclusions: The good concordance between the proportion of individuals with IFN‐γ release after SARS‐COV‐2 stimulation with the proportion of individuals with specific IFN‐γ+ CD8/CD4 T cells found in this study drives IFN‐γ release assays to be a simple and easy way to determine the protective immunity to SARS‐CoV‐2 in a wide population. [ABSTRACT FROM AUTHOR]

In 2019, Cuba approved a new political constitution that calls for deepening citizen participation to strengthen local governance. The emerging decentralization processes and the role of new actors in urban development open new possibilities for inclusive planning. While citizen participation is widely documented in the global South and under Western liberal democracy regimes, participatory urban planning in the context of Southern socialist cities such as Havana has been less scrutinized. This paper aims at mapping the framings, trajectories and legacies of such participatory planning initiatives. Based on mapping workshops and desktop research, we find that participatory initiatives within Havana are spatially dispersed, sporadic, lacking at the city level, and occurring in isolation at the neighbourhood level. We argue that establishing sustained participatory urban planning practices in Havana requires decision makers to scale outwards and upwards the lessons learned from existing initiatives to foster a city-wide participatory planning strategy. [ABSTRACT FROM AUTHOR]

Objectives: Antibody response to the first dose of BNT162b2 SARS‐CoV‐2 is greater in COVID‐19‐convalescent than in infection‐naïve individuals. However, there are no data about T‐cell response in individuals with pre‐existing cellular immunity. Methods: We evaluated T‐cell responses in parallel with SARS‐CoV‐2 antibody level after first dose of BNT162b2 vaccine in 23 infection‐naïve and 27 convalescent healthcare workers (HCWs) previously included in a study about humoral and T‐cell immunity. Results: Overall, the antibody response was lower in the infection‐naïve group than in convalescent individuals (18 895 vs 662.7 AU mL−1, P < 0.001), and intermediate but significantly lower in convalescent HCWs with previous negative serology (25 174 vs 1793 AU mL−1; P = 0.015). Indeed, anti‐spike IgG titres after the first dose correlated with baseline anti‐nucleocapsid IgG titres (rho = 0.689; P < 0.001). Pre‐existing T‐cell immunity was observed in 78% of convalescent and 65% of the infection‐naïve HCWs. T‐cell response after the first dose of the vaccine was observed in nearly all the cases with pre‐existing T‐cell immunity, reaching 94% in convalescent HCWs and 93% in those with cross‐reactive T cells. It was lower in the infection‐naïve group (50%; P = 0.087) and in convalescent HCWs with negative serology (56%; P = 0.085). Notably, systemic reactogenicity after vaccination was mainly observed in those with pre‐existing T‐cell immunity (P = 0.051). Conclusion: Here, we report that the first dose of BTN162b2 elicits a similar S‐specific T‐cell response in cases of either past infection or cross‐reactive T cells, but lower in the rest of infection‐naïve individuals and in convalescent HCWs who have lost detectable specific antibodies during follow‐up. [ABSTRACT FROM AUTHOR]

We investigated the duration of humoral and T-cell immune response in paired samples among 22 convalescent healthcare workers (HCWs). A median of 1.8 months after diagnosis, T-cell response was significantly lower in HCWs with early loss of antibodies (6 cases [27%]). After 5.1 months, antibody decline was observed in 77% of cases (41% seroreverted; P < .01), and 36% had lost T-cell response (75% lost response to spike protein). Persistence of immune response was observed in those who developed a greater adaptive immune response. Our data point to the initial immune response as the relevant player in coronavirus disease 2019 duration of protection. [ABSTRACT FROM AUTHOR]

Abstract Background Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations. Methods Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA. Results From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I. Conclusions The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.

Human immunodeficiency virus (HIV) infection impairs mucosal immunity and leads to bacterial translocation, fueling chronic inflammation and disease progression. While this is well established, questions remain about the compositional profile of the translocated bacteria, and to what extent it is influenced by antiretroviral therapy (ART). Using 16S ribosomal DNA targeted sequencing and shotgun proteomics, we showed that HIV increases bacterial translocation from the gut to the blood. HIV increased alpha diversity in the blood, which was dominated by aerobic bacteria belonging to Micrococcaceae (Actinobacteria) and Pseudomonadaceae (Proteobacteria) families, and the number of circulating bacterial proteins was also increased. Forty-eight weeks of ART attenuated this phenomenon. We found that enrichment with Lactobacillales order, and depletion of Actinobacteria class and Moraxellaceae and Corynebacteriacae families, were significantly associated with greater immune recovery and correlated with several inflammatory markers. Our findings suggest that the molecular cross talk between the host and the translocated bacterial products could influence ART-mediated immune recovery. [ABSTRACT FROM AUTHOR]