Sex: F
Vaccine: COVID19, UNK, UNK, UNK
Symptoms: Serology test, Vaccine induced antibody absent, White blood cell count
Clinical narrative: failure to elicit detectable circulating vaccine-specific IgG or IFN-? T cell responses/ lack of response/ vaccine hyporesponsiveness; failure to elicit detectable circulating vaccine-specific IgG or IFN-? T cell responses/ lack of response/ vaccine hyporesponsiveness; This is a literature report from a regulatory authority.  This spontaneous case was reported in the medical literature by a physician and concerns a 74-year-old female patient, who experienced serious adverse reaction of failure to elicit detectable circulating vaccine-specific IgG or IFN-Gamma T cell responses/ lack of response/ vaccine hyporesponsiveness associated with mycophenolate sodium, prednisone, eculizumab and COVID-19 MRNA VACCINE (NUCLEOSIDE-MODIFIED) along with peripheral blood lymphopenia associated mycophenolate sodium. The patient was diagnosed with generalized Myasthenia gravis (MG) 44 months prior to initial SARS-CoV-2 vaccination. Serologic testing showed elevated antibodies to acetylcholine receptors. For 18 months prior to and including the vaccine time course, treatment with 1440 mg mycophenolate sodium and prednisone 11 mg daily resulted in clinically stability. There was a remote history of ductal carcinoma in situ and Hashimoto's thyroiditis, and no history of opportunistic infection. Peripheral blood monitoring showed 8700 leukocytes and 800 lymphocytes per microliter (9%), consistent with mild lymphopenia. Three months prior to initial vaccination, the patient began treatment with eculizumab, an anti-C5 monoclonal antibody with activity in MG. Eculizumab was given weekly and then biweekly per labelling. The indication was adjunctive therapy to bridge elective surgery, which was uneventful. Eight weeks after surgery, BNT162b2 vaccination was started and two doses were administered 21 days apart. Eculizumab administration time points included 10 days prior to dose 1 of BNT162b2 and 3 days prior to dose 2, with the last dose given 11 days later. Blood was initially tested 71 days after the second dose of BNT162b2. The SARS-CoV-2 RBD binding antibody level was 19 arbitrary units (AU)/ml, with values below 50 considered negative. QuantiFERON SARS-CoV-2 RUO (Qiagen), an S-peptide-based interferon- Gamma release assay (IGRA) similar to the QFT-Plus assay for Mycobacterium tuberculosis-specific T cells, was performed per the manufacturer. SARS-CoV-2 S peptide pool S1 and S2 net values of 0.02 international units (IU)/ml and 0.03 IU/ml were summed to 0.05 IU/ml to provide a single metric. Negative (nil) and positive (mitogen) control values were 0.02 IU/ml and >10 IU/ml, indicating negligible background lymphocyte activation and intact activation potential. Amongst 14 healthy controls (HC) studied a median of 58 days (range, 10-107) after completing BNT162b2 (10 persons) or M1273 (4 persons), median net summary response to S was 1.27 IU/ml (range, 0.34 IU/ml-2.60 IU/ ml). HC median nil was 0.03 IU/ml (range, 0.02 IU/ml-0.06 IU/ml) and each mitogen control was >10 IU/ml. After tests for vaccine immunogenicity returned negative, the patient sought repeat vaccination. At 85 days after completing BNT162b2, the patient received M1273, with a second dose 29 days later. Side effects were minimal. Immune response were tested 16 days after the second dose of M1273. The serum anti-SARS-CoV-2 RBD IgG level was 2999 AU/ml, considered positive. IGRA re-test 32 days after completing M1273 showed a net summary response to S peptides of 0.38 IU/ml IFN-Gamma, with nil and mitogen responses of 0.03 IU/ml and >10 IU/ml. The authors present a case of a patient with MG receiving mycophenolate, prednisone, and eculizumab in whom mRNA vaccination failed to elicit detectable circulating vaccine-specific IgG or IFN-Gamma T cell responses. Eculizumab was discontinued, and repeat vaccination with two doses of an alternative EUA mRNA vaccine led to circulating IgG specific for the receptor binding domain (RBD) of the SARSCoV- 2 spike (S) protein, and to detectable S-specific T cell responses. While it is not known if these responses will protect against SARS-CoV-2 infection or disease, a repeat course of mRNA vaccination appears to be safe and was broadly immunogenic in this individual. Mycophenolic acid is an antagonist of inosine-5-monophosphate dehydrogenase that inhibits lymphocyte proliferation. Use can lead to peripheral blood lymphopenia, a variety of opportunistic infections, and poor responsiveness to vaccines including SARS-CoV-2 mRNA vaccination. Corticosteroids such as prednisone have myriad effects including susceptibility to infection and diminished vaccine immunogenicity. In summary, two doses of M1273, three months after a standard course of BNT162b2, resulted in peripheral T- and B-cell conversion in a person dependent on mycophenolate and prednisone therapy to maintain MG clinical remission. A contribution of the transient eculizumab therapy to the lack of response to BNT162b2 cannot be ruled out, but vaccine hyporesponsiveness was more likely related to mycophenolate and prednisone. Follow-up information has been requested.; Sender's Comments: Based on the information provide and plausible temporal association, the causality between BNT162B2 and Decreased immune responsiveness, Vaccine induced antibody absent cannot be completely excluded. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.