Immunization of immunosuppressed patients - Knowledge, practice and serological response
In this PhD-study the immunological response to pneumococcal vaccination with the prime-boost combination of the protein conjugated 13-valent vaccine, Prevenar13®, and the 23-valent polysaccharide vaccine, Pneumovax®, will be investigated in a randomized clinical trial in kidney transplant recipients. The study will include patients from Odense University Hospital, Roskilde Hospital and Rigshospitalet.
The group of immunocompromised patients is increasing rapidly and covers a wide range of conditions, among these are patients with transplants, people infected with HIV, splenectomised as well as patients with autoimmune inflammatory diseases undergoing treatment with biological drugs or other immune-suppressants. These patients comprise a diverse group of people and the degree of immune impairment is variable, yet they are all considered immunocompromised rendering them more vulnerable to infections.
Several of these infections are preventable by use of existing vaccines. However, there still seems to be an unmet demand for greater awareness of these needs, and vaccination coverage in immunocompromised patients remains insufficient.
The vaccine requirements for immunocompromised people differ from that of immunocompetent people. Most "routine" vaccinations are administered during childhood, but some require boosting during adulthood, whilst others are indicated due to travelling or increased susceptibility. While vaccinations are generally most likely to generate the best serological response when the immunofunction is close to normal, the risk of infection - or reactivation of a chronic infection and need of prophylaxis - is highest in those with more severe immunosuppression.
In particular, infection caused by influenza virus and Streptococcus pneumoniae can cause significant morbidity and mortality, and reactivation of chronic viruses such as VZV and HBV can cause severe disease in immunosuppressed persons.
The current recommendation regarding pneumococcal vaccination for adult risk groups is a prime-boost pneumococcal vaccination with PCV-13 followed by PPV-23 8 weeks later. Several studies have demonstrated a better response to serotypes common to both vaccines when PCV-13 is administered before PPV-23, and a superior effect of PCV-13 in adults was recently demonstrated in the large CAPITA study. The rationale behind this is that unlike PPV-23, PCV-13 induces a T-cell-dependent immune response. However, the optimal dose and interval for PCV-13 followed by PPV-23 has not been specifically studied, as well as the optimal use and clinical impact in kidney transplant recipients. There is a need for studies to examine the potential benefit and efficacy of vaccinations, and their optimal timing, both regarding 1) dose and intervals between the two vaccines and 2) the time after transplantation and degree of immunosuppression. Hopefully, these studies will inform guidelines and provide even better vaccination strategies in order to enhance the coverage in immunosuppressed patients.
Description of the cohort
We wish to enroll approximately 100 renal transplant recipients and 100 End Stage Renal Disease (ESRD) patients awaiting renal transplantation.
Data and biological material
Primary response variables: Pneumococcal vaccine response, immunological surrogate markers: pneumococcal serotype-specific IgG serum concentration for 12 serotypes. We will use the reference value 1µg/mL or a 2-fold rise in pneumococcal IgG serum concentration as a significant serological response to the pneumococcal vaccines.
Explanatory variables: The following information may be of importance for the immunological response: age, gender, former vaccination status of pneumococcal and influenza (year, number), BMI, ethnicity, smoking, alcohol; co-morbidities, including: COPD, ischemic heart disease, DM, Hepatitis C/B, CMV seropositivity; immunosuppressive therapy and time since transplantation.
Collaborating researchers and departments
Department of Infectious Diseases, Odense University Hospital and University of Southern Denmark
- PhD student Lykke Larsen, MD
- Professor Isik Somuncu Johansen, MD, DMSc.
- Professor Court Pedersen, MD, DMSc.
Department of Nephrology, Odense University Hospital
Department of Nephrology, Rigshospitalet
- Professor Søren Schwartz Sørensen, MD, DMSc.
Department of Medicin, Roskilde Hospital
- Senior Consultant Tina Berg Jensen
Publications associated with the project
Lykke Larsen, Mai Thanh Thuy Nguyen & Isik Somuncu Johansen (2021) The coverage of influenza and pneumococcal vaccinations among people living with HIV in Denmark: A single-center cross-sectional survey, Human Vaccines & Immunotherapeutics, 17:8, 2700-2705, DOI: 10.1080/21645515.2021.1894895
Larsen L, Bistrup C, Sørensen SS, Boesby L, Nguyen MTT, Johansen IS. The coverage of influenza and pneumococcal vaccination among kidney transplant recipients and waiting list patients: A cross-sectional survey in Denmark. Transpl Infect Dis. 2021 Jun;23(3):e13537. doi: 10.1111/tid.13537. Epub 2020 Dec 17. PMID: 33258216.