Residual susceptibility to measles among young adults in Victoria, Australia following a national targeted measles-mumps-rubella vaccination campaign

<p>Abstract</p> <p>Background</p> <p>Past measles immunisation policies in Australia have resulted in a cohort of young adults who have been inadequately vaccinated, but who also have low levels of naturally acquired immunity because immunisation programs have decreased the circulation of wild virus. A measles-mumps-rubella (MMR) immunisation campaign aimed at addressing this susceptibility to measles among young adults was conducted in Australia in 2001–2. By estimating age-specific immunity, we aimed to evaluate the success of this campaign in the state of Victoria.</p> <p>Methods</p> <p>We conducted serosurveys after the young adult MMR program at state and national levels to estimate immunity among young adults born between 1968–82. We compared results of the Victorian (state) surveys with the Victorian component of the national surveys and compared both surveys with surveys conducted before the campaign. We also reviewed all laboratory confirmed measles cases in Victoria between 2000–4.</p> <p>Results</p> <p>The Victorian state serosurveys indicated no significant change in immunity of the cohort following the young adult MMR campaign (83.9% immune pre and 85.5% immune post campaign) while the Victorian component of the national serosurvey indicated a significant decline in immunity (91.0% to 84.2%; p = 0.006). Both surveys indicated about 15% susceptibility to measles among young Victorian adults after the campaign. Measles outbreaks in Victoria between 2000–4 confirmed the susceptibility of young adults. Outbreaks involved a median of 2.5 cases with a median age of 24.5 years.</p> <p>Conclusion</p> <p>In Victoria, the young adult MMR program appears to have had no effect on residual susceptibility to measles among the 1968–82 birth cohort. Young adults in Victoria, as in other countries where past immunisation policies have left a residual susceptible cohort, represent a potential problem for the maintenance of measles elimination.</p

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan

CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M158–66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αβ signatures. Suboptimal TCRαβ signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections

Robust SARS-CoV-2 T cell responses with common TCR?? motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response

Development of a Real-Time PCR Assay To Detect Treponema pallidum in Clinical Specimens and Assessment of the Assay's Performance by Comparison with Serological Testing

The incidence of infectious syphilis in men who have sex with men and human immunodeficiency virus-infected patients has increased steadily in Victoria, Australia, since 2002. A TaqMan real-time PCR assay targeting the polA gene of Treponema pallidum (TpPCR) was developed. The analytical sensitivity of the assay was estimated to be 1.75 target copies per reaction. Initially, the assay was used to test a variety of specimens (excluding blood) from 598 patients. Of the 660 tests performed, positive PCR results were obtained for 55 patients. TpPCR results were compared with serology results for 301 patients being investigated for early syphilis. Of these patients, 41 were positive by both TpPCR and serology, 246 were negative by both TpPCR and serology, 4 were TpPCR positive but negative by serology, and 10 were TpPCR negative but showed evidence of recent or active infection by serology. Directly compared with serology, TpPCR showed 95% agreement, with a sensitivity of 80.39% and a specificity of 98.40%. Potential factors leading to the discrepant results are discussed. Concurrent serology on 21 patients with TpPCR-positive primary syphilitic lesions demonstrated that a panel of current syphilis serological tests has high sensitivity for the detection of early syphilis. We found that TpPCR is a useful addition to serology for the diagnosis of infectious syphilis. Direct comparison with other T. pallidum PCR assays will be required to fully assess the limitations of the assay

Evaluation of 6 Commercial SARS-CoV-2 Serology Assays Detecting Different Antibodies for Clinical Testing and Serosurveillance.

BACKGROUND: Serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complements nucleic acid tests for patient diagnosis and enables monitoring of population susceptibility to inform the coronavirus disease 2019 (COVID-19) pandemic response. It is important to understand the reliability of assays with different antigen or antibody targets to detect humoral immunity after SARS-CoV-2 infection and to understand how antibody (Ab) binding assays compare to those detecting neutralizing antibody (nAb), particularly as we move into the era of vaccines. METHODS: We evaluated the performance of 6 commercially available enzyme-linked immunosorbent assays (ELISAs), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total or nAb. A result subset was compared with a cell culture-based microneutralization (MN) assay. We tested sera from patients with prior reverse transcription polymerase chain reaction-confirmed SARS-CoV-2 infection, prepandemic sera, and potential cross-reactive sera from patients with other non-COVID-19 acute infections. RESULTS: For sera collected &gt;14 days post-symptom onset, the assay achieving the highest sensitivity was the Wantai total Ab at 100% (95% CI, 94.6%-100%), followed by 93.1% for Euroimmun NCP-IgG, 93.1% for GenScript sVNT, 90.3% for Euroimmun S1-IgG, 88.9% for Euroimmun S1-IgA, and 83.3% for Wantai IgM. Specificity for the best-performing assay was 99.5% for the Wantai total Ab, and for the lowest-performing assay it was 97.1% for sVNT (as per the Instructions for Use [IFU]). The Wantai Total Ab had the best agreement with MN at 98% followed by Euroimmun S1-IgA, Euro NCP-IgG, and sVNT (as per IFU) with 97%, 97% and 95%, respectively; Wantai IgM had the poorest agreement at 93%. CONCLUSIONS: Performance characteristics of the SARS-CoV-2 serology assays detecting different antibody types are consistent with those found in previously published reports. Evaluation of the surrogate virus neutralization test in comparison to the Ab binding assays and a cell culture-based neutralization assay showed good result correlation between all assays. However, correlation between the cell-based neutralization test and some assays detecting Abs not specifically involved in neutralization was higher than with the sVNT. This study demonstrates the reliability of different assays to detect the humoral immune response following SARS-CoV-2 infection, which can be used to optimize serological test algorithms for assessing antibody responses post-SARS-CoV-2 infection or vaccination

Prospective comprehensive profiling of immune responses to COVID‐19 vaccination in patients on zanubrutinib therapy

Abstract Zanubrutinib‐treated and treatment‐naïve patients with chronic lymphocytic leukaemia (CLL) or Waldenstrom's macroglobulinaemia were recruited in this prospective study to comprehensively profile humoral and cellular immune responses to COVID‐19 vaccination. Overall, 45 patients (median 72 years old) were recruited; the majority were male (71%), had CLL (76%) and were on zanubrutinib (78%). Seroconversion rates were 65% and 77% following two and three doses, respectively. CD4+ and CD8+ T‐cell response rates increased with third dose. In zanubrutinib‐treated patients, 86% developed either a humoral or cellular response. Patients on zanubrutinib developed substantial immune responses following two COVID‐19 vaccine doses, which further improved following a third dose