SUSPECTED IMMUNOLOGICAL VACCINE FAILURE; This solicited report received from a health care professional via NON-COMPANY STUDY: No Description Available, also referenced in literature. The objective of this article was aimed to investigate potential correlations between clinical, demographic, and immunological variables in MS patients to post-vaccination spike protein antibody positivity rates and levels. As per article, there was an analysis conducted with 50 patients and among these patients, 39/50 (78%) were white, 39/50 (78%) were female and the mean age was 53 to 55 years old. Out of 50 patients, 46 patients received mRNA vaccine (30 Pfizer/BioNTech and 16 Moderna) and 4 patients (8%) received the viral vector based vaccine (Janssen). 27 patients receiving B-cell therapy including ocrelizumab (18 patients), rituximab (8 patients), and ofatumumab (1 patient) at the time of vaccination. 10 patients (20%) were receiving fumarates. 4 patients (8%) receiving sphingosine-1-phosphate (S1P) modulators including fingolimod (1 patient) and siponimod (3 patients). 6 patients (12%) were receiving other immunomodulators including mycophenolate (3 patients), glatiramer acetate (1 patients), cladribine (1 patients), and satralizumab (1 patient). 3 patients were not receiving DMT (dimethyltryptamine) at the time of vaccination. Out of 50 patients, 29 patients tested positive for SARS-CoV2 spike antibody after vaccination with an mRNA or viral vector vaccine remaining are negative. Hypogammaglobulinemia (IgG less than 600 mg/dL) was associated with lower mean antibody levels (p value equal to 0.045) despite being noncontributory to positive/negative vaccine response. Authors found no relationship between lymphopenia and average antibody level (p value equal to 0.359). Most patients (98%), including those with negative humoral response, did not develop confirmed or suspected COVID19 infection after vaccine completion over an average follow-up of 3.7 months. Two patients had a pre-vaccine PCR-confirmed COVID-19 infection. 2 patients who received JNJ vaccine and showed Negative SARS-COV2 spike protein antibody out of 21. In the article, it was reported that two patients developed symptomatic noncomplicated COVID19 infection between the first and second vaccine doses. One of these patients was not on DMT at the time of vaccination however stopped mycophenolate 3 months prior to vaccination and started ocrelizumab two months after vaccination then eventually developed positive post-vaccination humoral response. The second patient was receiving rituximab at the time of vaccination and did not develop the antibody after the second vaccine dose. One patient on ocrelizumab received two doses of the Pfizer/BioNTech vaccine without spike antibody response 30 days after the second dose of the series. This patient received a third dose of the Pfizer/BioNTech vaccine six months after completing the initial series, however contracted a symptomatic non-complicated COVID-19 infection six weeks after the vaccine's third dose. Interestingly, this patient was tested for SARS-CoV2 spike protein antibody two weeks after recovery from the natural infection and had seroconverted to positive antibody status.  This report concerned an adult multiple patients (2) of age 6 decade. The patient's height, and weight were not reported. The patient's concurrent conditions included: relapsing remitting multiple sclerosis (25 patients), secondary progressive multiple sclerosis (8 patients), neuromyelitis optica spectrum disorder (7 patients), primary progressive multiple sclerosis (6 patients), central nervous system vasculitis (3 patients), chronic relapsing inflammatory optic neuropathy (1 patient), lymphopenia (11 patients), and hypogammaglobulinemia (unspecified). The patients received covid-19 vaccine ad26.cov2.s (suspension for injection, route of admin, and batch number and expiry date were not reported) dose, start therapy date were not reported, 1 total for prophylactic vaccination. The batch number was not reported and has been requested. Concomitant medications included cladribine, dimethyltryptamine, fingolimod, glatiramer acetate, mycophenolate mofetil, ocrelizumab, ofatumumab, rituximab, satralizumab, and siponimod.  On an unspecified date, 2 patients experienced suspected immunological vaccine failure. Laboratory data (dates unspecified) included: COVID-19 antibody test (NR: not provided) negative (negative for 2 patients and the Latency was at least 14 days). Blood samples were collected by venipuncture at least 14 days after the first dose of adenovirus vector vaccine (Janssen). The action taken with covid-19 vaccine ad26.cov2.s was not applicable. The outcome of suspected immunological vaccine failure was not reported. The reporter provided no causality assessment. Company causality between covid-19 vaccine ad26.cov2.s, and suspected immunological vaccine failure was not related. The authors concluded that B-cell therapy is associated with a negative humoral response to SARS-COV-2 vaccines. Patients on B-cell depleting therapy with detectable CD19 counts at the time of vaccination were associated with a positive humoral response. There was no relationship between hypogammaglobinemia and seroconversion rate, however it was associated with decreased spike protein antibody levels. The fumarates are associated with positive humoral response even in the presence of mild lymphopenia. This report was serious (Other Medically Important Condition). This report was associated with a product quality complaint and reference number was requested.; Sender's Comments: V0: 20220452162- covid-19 vaccine ad26.cov2.s - suspected immunological vaccine failure. 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. Therefore, this event(s) is considered not related.