Vaccine-induced Immunity in Immunocompromised Patients

Overview

Managing respiratory virus infections in immunocompromised patients requires a multidisciplinary approach, including vaccination, though its effectiveness is often suboptimal in these individuals. In hematological patients, poor humoral immunogenicity is common, especially when the B cell axis is affected by disease or treatment, while T cell responses may offer better protection. Current immunologic data on these patients is limited, focusing mostly on serologic parameters. To address this, we will conduct an observational study analyzing early and late booster vaccinations, with a focus on virus-specific T cell responses in vaccinated patients.

Respiratory virus infections are a significant cause of morbidity and mortality, partic-ularly among immunocompromised patients. These infections are caused by a varie-ty of viral pathogens, including influenza viruses, respiratory syncytial virus (RSV), parainfluenza viruses, adenoviruses, rhinoviruses, and coronaviruses, among oth-ers. In the general population, these infections typically result in self-limiting ill-nesses; however, in individuals with compromised immune systems, such as those undergoing chemotherapy, organ transplant recipients, patients with haematological malignancies, and those with HIV, the consequences can be severe and often life-threatening. For example, patients with haematological and oncological diseases are at elevated risk for severe morbidity and mortality by influenza infections. Com-pared to influenza-associated hospitalization rates in the general population (37.9 per 100,000 person-years for persons age 50 to 64 years)1 patients with cancer were hospitalized at a rate of 219 per 100,000 person-years for patients younger than 65 years. The immune system plays a crucial role in defending against viral pathogens. Im-munocompromised patients, due to either primary immune deficiencies or second-ary immunosuppression (e.g., from immunosuppressive therapies), have impaired immune responses that hinder the effective clearance of viral infections. This im-pairment can lead to prolonged viral shedding, increased risk of secondary bacterial infections, and more severe disease manifestations, including acute respiratory dis-tress syndrome (ARDS) and multi-organ failure. The management of respiratory vi-rus infections in immunocompromised patients requires a multidisciplinary ap-proach. Prophylactic measures, including vaccination and the use of antiviral prophylaxis, are crucial in reducing the incidence of these infections. Given the significant impact of respiratory virus infections on immunocompromised patients, ongoing research is crucial to improve preventive strategies. This research includes studies on viral pathophysiology, host immune responses, and the devel-opment of optimal vaccination schedules. The emergence of new viral pathogens, such as SARS-CoV-2, underscores the importance of surveillance and prepared-ness in this vulnerable population. Respiratory virus infections represent a major health concern for immunocompro-mised patients, necessitating comprehensive and specialised care. Continued ad-vancements in diagnostics, therapeutics, and preventive measures are vital to miti-gate the impact of these infections and improve the quality of life and survival of immunocompromised individuals. The management of respiratory virus infections in immunocompromised patients requires a multidisciplinary approach and prophylactic measures, including vaccina-tion, to reduce the incidence and severity of these infections. However, the efficacy of vaccination is often suboptimal in immunocompromised individuals and not well assessed in clinical trials. A poor humoral immunogenicity has been shown for most available vaccines in haematological patients. Especially affection of the B cell axis by either disease, treatment, or both, impacts humoral vaccine immune response. The humoral vaccine-induced immune response facilitates early protection directly after vaccination, while long-term protection warrants antibody persistence as well as immune memory cells. Data from immunocompetent persons suggest that cell mediated immune response may be a better correlate of protection against virus in-fections in vaccinated patients with poor immune responses than humoral im-munity due to its major role in recovery from infection and in virus clearance. Immunologic data in patients with haematological malignancies are generally scarce and mainly focus on serologic parameters. However, cellular response and especially T cell response seems often to be induced more reliably in those patients than humoral response as seen in other immunocompromised populations18 and other vaccines. To close this knowledge gap, we will perform an observational study to prospectively analyse the effect of early and late booster vaccination with special focus on the virus-specific T cells. Samples will be collected from patients that have been vac-cinated as part of clinical routine.