SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire.

Little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS2) vaccine breakthrough infections (BTIs) on the magnitude and breadth of the T cell repertoire after exposure to different variants. We studied samples from individuals who experienced symptomatic BTIs during Delta or Omicron waves. In the pre-BTI samples, 30% of the donors exhibited substantial immune memory against non-S (spike) SARS2 antigens, consistent with previous undiagnosed asymptomatic SARS2 infections. Following symptomatic BTI, we observed (1) enhanced S-specific CD4 and CD8 T cell responses in donors without previous asymptomatic infection, (2) expansion of CD4 and CD8 T cell responses to non-S targets (M, N, and nsps) independent of SARS2 variant, and (3) generation of novel epitopes recognizing variant-specific mutations. These variant-specific T cell responses accounted for 9%-15% of the total epitope repertoire. Overall, BTIs boost vaccine-induced immune responses by increasing the magnitude and by broadening the repertoire of T cell antigens and epitopes recognized.

Policing Practices and Risk of HIV Infection Among People Who Inject Drugs.

Drug-law enforcement constitutes a structural determinant of health among people who inject drugs (PWID). Street encounters between police and PWID (e.g., syringe confiscation, physical assault) have been associated with health harms, but these relationships have not been systematically assessed. We conducted a systematic literature review to evaluate the contribution of policing to risk of human immunodeficiency virus (HIV) infection among PWID. We screened MEDLINE, sociological databases, and gray literature for studies published from 1981 to November 2018 that included estimates of HIV infection/risk behaviors and street policing encounters. We extracted and summarized quantitative findings from all eligible studies. We screened 8,201 abstracts, reviewed 175 full-text articles, and included 27 eligible analyses from 9 countries (Canada, China, India, Malaysia, Mexico, Russia, Thailand, Ukraine, and the United States). Heterogeneity in variable and endpoint selection precluded meta-analyses. In 5 (19%) studies, HIV infection among PWID was significantly associated with syringe confiscation, reluctance to buy/carry syringes for fear of police, rushed injection due to a police presence, fear of arrest, being arrested for planted drugs, and physical abuse. Twenty-one (78%) studies identified policing practices to be associated with HIV risk behaviors related to injection drug use (e.g., syringe-sharing, using a "shooting gallery"). In 9 (33%) studies, policing was associated with PWID avoidance of harm reduction services, including syringe exchange, methadone maintenance, and safe consumption facilities. Evidence suggests that policing shapes HIV risk among PWID, but lower-income settings are underrepresented. Curbing injection-related HIV risk necessitates additional structural interventions. Methodological harmonization could facilitate knowledge generation on the role of police as a determinant of population health.