SUSPECTED IMMUNOLOGICAL VACCINE FAILURE; INTENTIONAL PRODUCT MISUSE; OFF LABEL USE; This spontaneous report was received from literature. This report concerned a 9 decade old female of unspecified race and ethnic origin. The objective of this study was to describe Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients. The patient's height, and weight were not reported. The patient's concurrent conditions included: mild hypogammaglobulinemia, and chronic lymphocytic leukemia (CLL), and other pre-existing medical conditions included no history of recurring infections or need for IgG supplementation. The patient was previously treated with obinutuzumab. The patient received covid-19 vaccine ad26.cov2.s (suspension for injection, route of administration not reported, batch number: unknown) dose not reported, 1 total, start therapy date were not reported for prophylactic vaccination. The batch number was not reported and has been requested. Concomitant medications included BNT 162 for prophylactic vaccination, and ibrutinib. The patient self-referred and received covid-19 vaccine ad26.cov2.s 81 days after completion of the BNT162 vaccine series (intentional product misuse and off label use). After 27 days following third vaccine additional samples were taken. It was reported that patient did not had pre-vaccination B-cell responses as measured by RBD-specific antibodies or MBC (Memory B-Cells) and did not had virus-specific CD8+ response at baseline. The patient had spike peptide-reactive CD4+ T-cells at baseline these cells were unresponsive and did not expand following vaccination. In contrast, CD8+ responses were observed after mRNA vaccination in the patient. Approximately four weeks after initial vaccination the patient had detectable RBD-specific SARS-CoV-2 antibodies or MBCs. The had measurable vaccine-induced CD8+ T-cell responses following mRNA vaccination, although CD4+ responses did not appear to increase above the baseline. The patient did not seroconvert or had detectable virus specific MBCs after their primary mRNA vaccination series however had a spike-specific CD8+ T-cell response that further boosted after a 3rd dose and a virus-specific CD4+ response that didn't change following original vaccine series or 3rd dose of J&J. The patient had undergone previous treatment (6 years ago) with obinutuzumab an anti-CD20 mAb and is currently on active treatment with Ibrutinib, since 2017. Both had baseline B-cell frequencies outside of the normal range. The patient had a low percentage of naive B-cells (11.37) and MBCs (0.45). Although the patient had mild hypogammaglobulinemia, the patient did not had history of recurring infection or need for IgG supplementation. The Levels of baseline CD4+ and CD8+ T cells (absolute values) were also normal, prior to vaccination (data not presented). The patient had very low percentage of naive B cells which could explains the initial poor response to vaccination. The patient had an increase in virus specific CD8+ T-cells. The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The outcome of the suspected immunological vaccine failure, intentional product misuse and off label use was not reported. The author emphasized that 3rd vaccination against COVID-19 with the heterotypic vaccine Ad26COV2.s results in an immune response that was not observed following the recommended 2-dose mRNA vaccination series. This report was serious (Other Medically Important Condition). This report is associated with product quality complaint. This case, from the same reporter is linked to 20210944630.  Version created to amend previously reported information on 15-SEP-2021. Upon review the following information was amended: events captured as per updated record note (suspected immunological vaccine failure, intentional product misuse and off label use), seriousness upgraded, event (Medication error) removed.; Sender's Comments: V1: Version created to amend the events captured, event coding, seriousness and MAC. 20210944702-COVID-19 VACCINE AD26.COV2.S- Suspected Immunological vaccine failure. This event(s) is considered not related. The event(s) has a compatible/suggestive temporal relationship, is unlabeled, and has unknown scientific plausibility. There are other factors more likely to be associated with the event(s) than the drug. Specifically: SPECIAL SITUATIONS