SARS-CoV-2 vaccine rollout has coincided with the spread of variants of concern. We investigated if single dose vaccination, with or without prior infection, confers cross protective immunity to variants. We analyzed T and B cell responses after first dose vaccination with the Pfizer/BioNTech mRNA vaccine BNT162b2 in healthcare workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1.1.7 and B.1.351 spike mutations resulted in increased, abrogated or unchanged T cell responses depending on human leukocyte antigen (HLA) polymorphisms. Single dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.

BackgroundThe discovery that heterozygous missense mutations in the gene encoding triggering receptor expressed on myeloid cells 2 (TREM2) are risk factors for Alzheimer’s disease (AD), with only the apolipoprotein E (APOE) ε4 gene allele conferring a higher risk, has led to increased interest in immune biology in the brain. TREM2 is expressed on microglia, the resident immune cells of the brain and has been linked to phagocytotic clearance of amyloid β (Aβ) plaques. Soluble TREM2 (sTREM2) has previously been measured in cerebrospinal fluid (CSF) by ELISA but in our hands commercial kits have proved unreliable, suggesting that other methods may be required. We developed a mass spectrometry method using selected reaction monitoring for the presence of a TREM2 peptide, which can be used to quantify levels of sTREM2 in CSF.FindingsWe examined CSF samples from memory clinics in Sweden and the UK. For all samples the following were available: clinical diagnosis, age, sex, and measurements of the CSF AD biomarkers Aβ42, T-tau and P-tau181. AD patients (n = 37) all met biomarker (IWG2) criteria for AD. Control individuals (n = 22) were cognitively normal without evidence for AD in CSF. We found significantly higher sTREM2 concentration in AD compared to control CSF. There were significant correlations between CSF sTREM2 and T-tau as well as P-tau181. CSF sTREM2 increase in AD was replicated in a second, independent cohort consisting of 24 AD patients and 16 healthy volunteers.ConclusionCSF concentrations of sTREM2 are higher in AD than in controls, and correlate with markers of neurodegeneration. CSF sTREM2 may be used to quantify glial activation in AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0071-x) contains supplementary material, which is available to authorized users.

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Periodontal disease is perhaps the most common infectious disease in humans. Gingival crevicular fluid (GCF) is a local inflammatory exudate of the periodontal tissues. Its composition greatly varies between health and periodontal disease. GCF collection is rapid and noninvasive, but previous approaches aiming to analyze its composition have mainly involved single protein biomarkers. The aim of this study was to perform analysis of the GCF exudatome from healthy and periodontally diseased sites by LC/MS E , a label-free mass spectrometry method that enables simultaneous protein identification and absolute quantification in biological fluids. In total, 154 proteins of human, bacterial, and viral origin were identified in the 40 GCF samples obtained from the 10 subjects (five healthy and five generalized aggressive periodontitis). The proportion of bacterial, viral, and yeast protein was increased in disease, compared to health. The presence of host defense-related proteins, such as Cystatin-B and defensins, was confirmed to be present only in health. Among the newly identified GCF proteins were L-plastin detected only in disease (15.6 ( 12.1 fmol) and Annexin-1 detected in 5-fold higher levels in health. Nevertheless, pro-inflammatory cytokines or periodontal pathogen proteins were rarely detected. Conclusively, the LC/MS E technology may facilitate characterization of GCF proteome in periodontal health and disease, thus conferring prognostic and diagnostic value. Larger cohort studies are required to characterize the complete GCF proteome in health and disease.