Background A third dose of measles-mumps-rubella vaccine (MMR3) is recommended in mumps outbreak scenarios, but the immune response and the need for widespread use of MMR3 remain uncertain. Herein, we characterized measles-specific immune responses to MMR3 in a cohort of 232 healthy subjects. Methods Serum and PBMCs were sampled at Day 0 and Day 28 after MMR3. Measles-specific binding and neutralizing antibodies were quantified in sera by ELISA and a microneutralization assay, respectively. PBMCs were stimulated with inactivated measles virus, and the release of cytokines/chemokines was assessed by a multiplex assay. Demographic variables of subjects were examined for potential correlations with immune outcomes. Results 95.69% and 100% of subjects were seropositive at Day 0 and Day 28, respectively. Antibody avidity significantly increased from 38.08% at Day 0 to 42.8% at Day 28 (p = 0.00026). Neutralizing antibodies significantly enhanced from 928.7 at Day 0 to 1,289.64 mIU/mL at Day 28 (p = 0.0001). Meanwhile, cytokine/chemokine responses remained largely unchanged. BMI was significantly correlated with the levels of inflammatory cytokines/chemokines. Conclusion Measles-specific humoral immune responses, but not cellular responses, were enhanced after MMR3 receipt, extending current understanding of immune responses to MMR3 and supporting MMR3 administration to seronegative or high-risk individuals.

The durability of protective humoral immunity after SARS-CoV-2 vaccination and infection is largely dependent on the generation and persistence of antigen-specific isotype-switched memory B cells (MBCs) and long-lived plasma cells that reside in the bone marrow and secrete high-affinity neutralizing antibodies. The reactivity of vaccine-induced MBCs to emerging clinically significant SARS-CoV-2 variants of concern (VoCs) is largely unknown. In a longitudinal cohort study (up to 6 months following COVID-19 mRNA vaccination) we measured MBCs in concert with other functional antibody measures. We found statistically significant differences between the frequencies of MBCs responding to homologous and VoC receptor-binding domain/RBDs (Beta, Gamma, and Delta) after vaccination that persisted over time. In concert with a waning antibody response, the reduced MBC response to VoCs could translate to a weaker subsequent recall immune response and increased susceptibility to the emerging SARS-CoV-2 variant strains after vaccination.

Abstract. Importance. A better understanding of the immune memory and functional humoral immunity directed at the emerging Variants of Concern (VoC) strains after SARS-CoV-2 vaccination is essential for predicting the longevity of heterotypic protection. Objective. The aim of our study was to characterize functional humoral immunity (including memory B cell response) after COVID-19 mRNA vaccination and to determine/compare the reactivity of COVID-19 vaccine-induced memory B cells to the emerging SARS-CoV-2 Variants of Concern (VoC). Design, setting, participants and interventions. We designed an exploratory longitudinal observational (convenience sample-based) study at Mayo Clinic, Rochester, MN that enrolled and followed naive subjects and recovered COVID-19 subjects from Olmsted County, MN and surrounding areas after COVID-19 vaccination in January-June 2021. The study enrolled 17 relatively healthy subjects, 59% females and 94% White/Non-Hispanic or Latino with median age at enrollment 41 years. The subjects received either the BNT162b2 (Pfizer/BioNtech) or mRNA-1273 (Moderna) vaccine (n=3) and provided a blood sample at baseline, at;3 weeks after their first vaccine dose/before the second dose, and at;2 weeks after the receipt of their second vaccine dose. Main outcomes and measures. Spike-specific humoral and memory B cells responses were assessed over time after vaccination against the original Wuhan-Hu-1/vaccine and against emerging VoC strains/antigens. Results. We observed a robust neutralizing antibody response after COVID-19 mRNA vaccination, but a reduction in the functional antibody activity to several of the emerging SARS-CoV-2 VoC. Consistent with this, we also found differences in the number of isotype-switched/IgG+ MBCs responding to homologous and variant receptor-binding domain/RBDs after vaccination. We found a reduction of MBCs reactive to RBDs of Beta, Gamma and Delta SARS-CoV-2 VoC strains. Conclusion and relevance. In this exploratory study in subjects following receipt of COVID-19 mRNA vaccine, we found differences in antibody titers observed for VoCs after vaccination that are accompanied with, and can partially be explained by, decreased MBC reactivity against the VoCs. This can further attenuate the generated recall humoral immune response upon exposure to these variants.

As water moves carbon through watersheds and across ecosystem boundaries, stream corridors collect and integrate landscape-scale signals of carbon cycling. Streams metabolize organic carbon and emit carbon dioxide (CO 2 ) and methane (CH 4 ) derived from internal metabolism and external sources (Hotchkiss et al., 2015;Stanley et al., 2016). The rates at which streams emit carbon to the atmosphere reflects their importance in local and global carbon cycling. Streams emit CO 2 globally at a rate that surpasses the terrestrial and oceanic carbon sinks (Webb et al., 2018) and emit approximately 5% of yearly global CH 4 to the atmosphere (Flury & Ulseth, 2019;Stanley et al., 2016). As global concentrations of atmospheric greenhouse gases continue to rise, quantifying the relative contributions of different sources and sinks of CO 2 and CH 4 grows ever more important.

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Background Despite extensive studies of human immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, research examining protective correlates of vertical transmission following maternal exposure in pregnancy remain limited. Here, we characterized antibody and cytokine responses in maternal and cord blood following infection or vaccination at various timepoints during gestation. Methods Spike S1 protein-specific binding antibodies and antibodies capable of blocking the interaction between the receptor binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) were measured in maternal and cord blood by ELISA. Serum concentrations of 74 cytokines/chemokines were measured by multiplex assay. Humoral responses and cytokine levels from matched maternal and fetal cord sera were compared and examined for potential correlations. Results We observed a highly significant correlation between Spike S1-specific antibody titer and RBD-ACE2 blocking antibody activity between maternal and fetal cord serum (p < 2.2e-16, R > 0.90). Blocking antibody activity was significantly higher for mothers infected during the 3rd trimester compared to earlier trimesters; however, vaccinated mothers developed and transferred higher antibody titers with greater RBD-ACE2 blocking antibody activity to their neonates than infected mothers. Furthermore, vaccine-induced Spike S1 IgG transfer ratios (fetal cord/maternal) were significantly higher than those induced by infection (p = 0.002). Multiplex assay showed significantly elevated levels of 33 cytokines/chemokines, mainly pro-inflammatory in infected maternal serum samples, while the paired fetal cord samples exhibited an anti-inflammatory cytokine predominance. Conclusion Our data support selective vertical transmission of potentially protective humoral responses against SARS-CoV-2, especially following vaccination in the 3rd trimester. The anti-inflammatory cytokine predominance in cord blood that persists despite maternal SARS-CoV-2 infection may offset the adverse outcomes of inflammation in pregnancy for the neonate. Disclosures All Authors: No reported disclosures.

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