SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

Abstract

BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11

Systemic and T cell‐associated responses to SARS‐CoV‐2 immunisation in gut inflammation (STAR SIGN study): effects of biologics on vaccination efficacy of the third dose of mRNA vaccines against SARS‐CoV‐2

“…First, we demonstrated that anti‐TNF treatment attenuates the anti‐spike IgG concentration following third dose vaccination, compared to treatment with non‐anti‐TNF biologics and healthy controls, respectively (Figure 2A,B). These observations are in line with findings from CLARITY‐IBD, VIP, PREVENT‐COVID, HERCULES and Wagner et al, while the STOP COVID‐19 in IBD study could not find reduced antibody concentrations in anti‐TNF‐treated IBD patients when comparing them to IBD patients without immunosuppressive treatment 24–26,28–30 . Importantly, it must be noted that the reduced antibody responses found in this study, might at least partially be influenced by already reduced antibody concentrations in anti‐TNF‐treated patients after two vaccine doses as shown before 10–12,31–37 …”

Humoral and cellular responses to mRNA-based COVID-19 booster vaccinations in patients with solid neoplasms under active treatment

“…higher binding and neutralizing antibody titers to the WT and omicron variant after booster, however 5-7x decrease in both after 2-4 months post booster Wagner A, et al Front Immunol. ( 44 ) BNT162b2, mRNA1273 4 weeks yes yes no 63 (breast or lung cancer) 49 (78%) under active treatment 0 66 Sign. higher antibody levels and neutralizing capacity after booster Zeng C, et al Cancer Cell.…”

Full seroconversion in initial non-responders with higher antibody levels after heterologous COVID-19 vaccination schedule.

“…Thus, these data further show that antibody testing is generally not needed to confirm seroconversion and vaccine responsiveness after primary COVID-19 vaccination in healthy individuals. However, in individuals under immunosuppressive therapies antibody testing is useful to identify vaccine non-responders [ 15 , 16 ] and guide further prophylactic treatment options such as application of monoclonal antibodies.…”