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Prioritizing Ontario’s long-term care home (LTCH) residents for vaccination against severe acute respiratory syndrome coronavirus 2 has drastically reduced their disease burden; however, recent LTCH outbreaks of variants of concern (VOCs) have raised questions regarding their immune responses. In 198 residents, mRNA vaccine dose 1 elicited partial spike and receptor binding domain antibody responses, while the second elicited a response at least equivalent to convalescent individuals in most residents. Residents administered mRNA-1273 (Moderna) mounted stronger total and neutralizing antibody responses than those administered BNT162b2 (Pfizer-BioNTech). Two to four weeks after dose 2, residents (n= 119, median age 88) produced 4.8–6.3-fold fewer neutralizing antibodies than staff (n= 78; median age 47) against wild-type (with D614G) pseudotyped lentivirus, and residents administered BNT162b2 produced 3.89-fold fewer neutralizing antibodies than those who received mRNA-1273. These effects were exacerbated upon serum challenge with pseudotyped VOC spike, with up to 7.94-fold reductions in B.1.351 (Beta) neutralization. Cumulatively, weaker vaccine stimulation, age/comorbidities, and the VOC produced an ∼130-fold reduction in apparent neutralization titers in LTCH residents and 37.9% of BNT162b2-vaccinated residents had undetectable neutralizing antibodies to B.1.351. Continued immune response surveillance and additional vaccine doses may be required in this population with known vulnerabilities.

COVID-19 is a respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We previously developed an enzyme-linked immunosorbent assay (ELISA) protocol to profile antibody responses to the SARS-CoV-2 Spike protein and its receptor-binding domain (RBD) in the saliva of patients with COVID-19. Anti-SARS-CoV-2 antibody responses were readily detected in saliva, peaking at 16–30 days post-symptom onset. While anti-SARS-CoV-2 IgM/IgA were found to decay, IgG responses were more long-lived, persisting up to 105 days. Now we wish to know (1) if anti-SARS-CoV-2 antibodies are generated locally in the oral cavity, (2) the relative kinetics of IgA versus IgG appearance in the oral cavity, and (3) whether salivary antibodies have the capacity to neutralize SARS-CoV-2. To answer these, I have adapted our ELISA to detect secretory component-associated SARS-CoV-2-specific antibodies. I found that 33.3% and 26.9% of COVID-19 patients were positive for secretory component-associated antibodies to Spike and RBD, respectively. Secretory component-associated antibodies correlated with antigen-specific IgA levels, particularly for the Spike antigen. Moreover, using saliva from contact-traced subjects, I found that anti-Spike/RBD IgM/IgA are detected in the saliva 7 days post-exposure, prior to IgG. Lastly, I detected Spike-specific antibody-secreting cells in lymphoid tissues draining the upper respiratory tract upon intranasal infection of K18-hACE2 mice with a non-lethal dose of SARS-CoV-2. In summary, I have provided evidence in humans and mice that a local antibody response that quickly class switches to IgA occurs in the oral cavity and draining lymph nodes upon infection with SARS-CoV-2.

In near-Earth space, the magnetosphere, energetic electrons (tens to thousands of kiloelectron volts) orbit around Earth, forming the radiation belts. When scattered by magnetospheric processes, these electrons precipitate to the upper atmosphere, where they deplete ozone, a radiatively active gas, modifying global atmospheric circulation. Relativistic electrons (those above a few hundred kiloelectron volts), can reach the lowest altitudes and have the strongest effects on the upper atmosphere; their loss from the magnetosphere is also important for space weather. Previous models have only considered magnetospheric scattering and precipitation of energetic electrons; atmospheric scattering of such electrons has not been adequately considered, principally due to lack of observations. Here we report the first observations of this process. We find that atmospherically-scattered energetic (relativistic) electrons form a low-intensity, persistent “drizzle”, whose integrated energy flux is comparable to (greater than) that of the more intense but ephemeral precipitation by magnetospheric scattering. Thus, atmospheric scattering of energetic electrons is important for global atmospheric circulation, radiation belt flux evolution, and the repopulation of the magnetosphere with lower-energy, secondary electrons.

South Asian (SA) Canadian immigrants have a higher risk of developing certain immune-mediated inflammatory diseases compared to non-migrant SAs. We sought to investigate the effect of migration on the gut metagenome and to identify microbiological associations between migration and conditions that may influence the development of immune-mediated inflammatory diseases. Metagenomic analysis of 58 first-generation (GEN1) SA immigrants and 38 unrelated Canadian born children-of-immigrants (GEN2) determined that the time lived in Canada was associated with continued changes in gut microbial communities. Migration of GEN1 to Canada early in life results in a gut community with similarities to GEN2 SA Canadians and non-SA North Americans. Conversely, GEN1 immigrants who arrived recently to Canada exhibited pronounced differences from GEN2, while displaying microbial similarities to a non-migrating SA cohort. Multivariate analysis identified that community composition was primarily influenced by high abundance taxa. Prevotella copri dominated in GEN1 and non-migrant SAs. Clostridia and functionally related Bacteroidia spp. replaced P. copri dominance over generations in Canada. Mutually exclusive Dialister species occurred at differing relative abundances over time and generations in Canada. This shift in species composition is accompanied by a change in genes associated with carbohydrate utilization and short-chain fatty acid production. Total energy derived from carbohydrates compared to protein consumption was significantly higher for GEN1 recent immigrants, which may influence the functional requirements of the gut community. This study demonstrates the associations between migration and the gut microbiome, which may be further associated with the altered risk of immune-mediated inflammatory diseases observed for SA Canadians.

The R620W variant of PTPN22 is one of the major genetic risk factors for several autoimmune disorders including type 1 diabetes (T1D) in humans. In the BioBreeding T1D-prone (BBDP) rat, a single nucleotide polymorphism in Ptpn22 results in an A629T substitution immediately C-terminal to the aliphatic residues central to the Ptpn22–C-terminal Src kinase interaction. This variant exhibits a 50% decrease in C-terminal Src kinase binding affinity and contributes to T cell hyperresponsiveness. Examination of BBDP sublines congenic for the Iddm26.2 locus that includes Ptpn22 has not only shown an expansion of activated CD4+25+ T lymphocytes in animals homozygous for the BBDP allele, consistent with enhanced TCR-mediated signaling, but also a decrease in their proportion of peripheral Foxp3+ regulatory T cells. Furthermore, clinical assessment of both an F2(BBDP × ACI.1u.Lyp) cohort and Iddm26.2 congenic BBDP sublines has revealed an association of Ptpn22 with T1D. Specifically, in both cases, T1D risk is significantly greater in BBDP Ptpn22 homozygous and heterozygous animals. These findings are consistent with a role for rat Ptpn22 allelic variation within Iddm26.2 in the regulation of T cell responses, and subsequently the risk for development of T1D.