Error bars represent SEM.cPie charts representing the relative proportions of Spike, M/N, or total (combined Spike and M/N) CD4 T-cell responses for one (gray), two (green) or three (dark blue) Albaspidin AA cytokines, and pie arcs denoting IFN-, TNF- and IL-2.dRepresentative flow cytometric plots for the identification of antigen-specific CD8 T cells based on Albaspidin AA the expression of (IFN-+, TNF-+, and IL-2+) against the specified peptide pools or media alone (control).eProportion of aggregated CD8 T-cell responses against Spike, M/N or combined (Spike and M/N) responses in HIV (n=12) and HIV+ (n=11) donors. T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH. Subject terms:Immunological memory, Antibodies, Viral infection, SARS-CoV-2 Understanding the pathology and immunological response to SARS CoV2 infection in specific patient groups is essential for informing the scientific and clinical handling of infections within these patient populations. Here the authors characterise the adaptive immune response to SARS-CoV2 infection in people living with HIV. == Introduction == The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19 disease, has resulted in an overall 3% case fatality rate, posing unprecedented healthcare challenges around the world1. With an evolving pandemic, urgent and efficient strategies are required for optimized interventions especially in patient populations with underlying chronic diseases. Nearly 40 million people are living with HIV (PLWH) worldwide and almost half of PLWH in Europe are over the age of 502. However, due to the scarcity of data, it remains unknown whether antiviral responses to SARS-CoV-2 are compromised and/or less durable in PLWH following primary infection. Mouse monoclonal to HK1 Such knowledge is crucial in the future clinical management of PLWH during the course of the pandemic and for informing strategies for vaccination programs. Epidemiological evidence indicates that the risk of severe COVID-19 disease increases with age, male gender, and in the presence of comorbidities3,4. PLWH, despite efficient virological suppression on antiretroviral treatment (ART), experience an increased burden of comorbid conditions associated with premature ageing5,6. These multi-morbidities are driven by residual inflammation on ART and ongoing immune dysregulation7that could influence COVID-19 disease severity, the durability of protective antiviral responses, which may prevent future re-infection, and responsiveness to vaccination8,9. Although there is no evidence of increased rates of COVID-19 disease among PLWH compared to the general population, mortality estimates vary between studies, with disparities in social health determinants and comorbidities likely having an influence1016. More recently, cellular immune deficiency and a lower CD4 T-cell count/low CD4 T-cell nadir have been identified as potential risk factors for severe SARS-CoV-2 infection in PLWH, irrespective of HIV virological suppression17. Burgeoning evidence supports a role for CD4 T cells in the control and resolution of acute SARS-CoV-2 infection1820, in addition to providing CD8 T cell and B cell help for long-term immunity21,22. Any pre-existing CD4 T-cell depletion in PLWH, as described in patients with hematological malignancy23, could therefore be a potential driver of dysregulated immunity to SARS-CoV-2, hampering Albaspidin AA antiviral responses24and development of immunological memory. Despite the collective efforts to define the correlates of immune protection and evaluate the durability of protective immune responses elicited post SARS-CoV-2 infection in the general population, reports in PLWH are limited. Overall, the majority of people infected with SARS-CoV-2 in the absence of HIV develop durable antibody responses including neutralizing antibodies and T-cell responses18,2528. In most cases the magnitude of humoral responses is complemented by multi-specific T-cell responses and appears to be dependent on the severity and protracted course of COVID-19 disease18,27,29. However, humoral and cellular immune responses are not always correlative, with T-cell immunity being induced even in the absence of detectable antibodies during mild COVID-19 disease18,30,31and predicted to be more enduring from experience with other coronaviruses32,33. Notably, older individuals more often display poorly coordinated immune adaptive responses to SARS-CoV-2 associated with worse disease outcome18,34. This is particularly pertinent for PLWH, in whom the combined effect of ageing/premature immunosenescence and residual immune dysfunction in the era of effective ART could have important consequences for the development of immune responses to a new pathogen and vaccination35. To date, a single case report suggests a longer disease course and delayed antibody response against SARS-CoV-2 in HIV patients36, and a combined seroprevalence/PCR testing study suggested a diminished serological response in PLWH37. However, a simultaneous assessment of antibodies and T-cell responses in the convalescent phase of COVID-19 disease is lacking in PLWH. To address this knowledge gap, we performed an integrated cross-sectional analysis of different branches of adaptive immunity to SARS-CoV-2 in PLWH, controlled on ART, compared to. Albaspidin AA