Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab.

Introduction: Patients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment. Methods: We enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses. Results: At 30 days from the second dose, the median antibodies level in MM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARS-CoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of long-term humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection. Conclusion: Monitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease.

Associations of HLA Polymorphisms with Anti-SARS-CoV-2 Spike and Neutralizing Antibody Titers in Japanese Rheumatoid Arthritis Patients Vaccinated with BNT162b2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019. Anti-SARS-CoV-2 spike (S) and neutralizing antibodies (Abs) are measured to evaluate the efficacy of vaccines. Human leukocyte antigen (HLA) may be associated with vaccine efficacy. Here, we investigated the association of HLA polymorphisms with the production of anti-SARS-CoV-2 S or neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Genotyping of DRB1 and DQB1 was conducted in 87 Japanese RA patients vaccinated with BNT162b2. Associations of allele or haplotype carrier frequencies with anti-SARS-CoV-2 S or neutralizing Abs were examined. DRB1*12:01 was significantly positively associated with the production of S Ab (p = 0.0225, odds ratio [OR] 6.08, 95% confidence interval [CI] 1.32-28.03). The DQB1*03:01 allele carrier frequency tended to be higher in high responders of S Ab. Allele carrier frequencies of DRB1*15:01 (p = 0.0102, OR 9.26, 95% CI 1.65-52.01) and DQB1*06:02 (p = 0.0373, OR 7.00, 95% CI 1.18-41.36) were higher in responders of neutralizing Ab. Haplotype and two-locus analyses of DRB1 and DQB1 suggested that DRB1 alleles were the primary drivers of these associations. Logistic regression analysis showed associations of these alleles independent of clinical characteristics. Independent associations were found between HLA alleles and anti-SARS-CoV-2 Ab production by vaccinated RA patients.

Antibody-mediated immunity to SARS-CoV-2 spike.

Despite effective spike-based vaccines and monoclonal antibodies, the SARS-CoV-2 pandemic continues more than two and a half years post-onset. Relentless investigation has outlined a causative dynamic between host-derived antibodies and reciprocal viral subversion. Integration of this paradigm into the architecture of next generation antiviral strategies, predicated on a foundational understanding of the virology and immunology of SARS-CoV-2, will be critical for success. This review aims to serve as a primer on the immunity endowed by antibodies targeting SARS-CoV-2 spike protein through a structural perspective. We begin by introducing the structure and function of spike, polyclonal immunity to SARS-CoV-2 spike, and the emergence of major SARS-CoV-2 variants that evade immunity. The remainder of the article comprises an in-depth dissection of all major epitopes on SARS-CoV-2 spike in molecular detail, with emphasis on the origins, neutralizing potency, mechanisms of action, cross-reactivity, and variant resistance of representative monoclonal antibodies to each epitope.

GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine.

Background: Immune responses following vaccination against COVID-19 with different vaccines and the waning of immunity vary within the population. Genetic host factors are likely to contribute to this variability. However, to the best of our knowledge, no study on G protein polymorphisms and vaccination responses against COVID-19 has been published so far. Methods: Antibodies against the SARS-CoV-2 spike protein and T-cell responses against a peptide pool of SARS-CoV-2 S1 proteins were measured 1 and 6 months after the second vaccination with mRNA-1273 in the main study group of 204 participants. Additionally, antibodies against the SARS-CoV-2 spike protein were measured in a group of 597 participants 1 month after the second vaccination with mRNA-1273. Genotypes of GNB3 c.825C>T were determined in all participants. Results: The median antibody titer against the SARS-CoV-2 spike protein and median values of spots increment in the SARS-CoV-2 IFN-γ ELISpot assay against the S1-peptide pool were significantly decreased from months 1 to 6 (p < 0.0001). Genotypes of GNB3 c.825C>T had no influence on the humoral immune response. At month 1, CC genotype carriers had significantly increased T-cell responses compared to CT (p = 0.005) or TT (p = 0.02) genotypes. CC genotype carriers had an almost 6-fold increased probability compared to TT genotype carriers and an almost 3-fold increased probability compared to T-allele carriers to mount a SARS-CoV-2-specific T-cell response above the median value. Conclusion: CC genotype carriers of the GNB3 c.825C>T polymorphism have an increased T-cell immune response to SARS-CoV-2, which may indicate better T-cell-mediated protection against COVID-19 after vaccination with mRNA-1273.

Anti-SARS-CoV-2 Spike Antibody Titers and Neutralizing Antibodies in Vaccinated Rheumatoid Arthritis Patients.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A serological test is used to assess the efficacy of vaccination. It has been reported that anti-SARS-CoV-2 spike (S) and neutralizing antibody (Ab) levels are lower following vaccination in patients with rheumatic disease. Here, we investigated anti-SARS-CoV-2 S and neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Anti-SARS-CoV-2 S and neutralizing Abs were quantified in 101 RA patients and 117 controls. Anti-SARS-CoV-2 S Ab levels were lower in RA patients than both earlier after vaccination in controls (mean RA 324.1 ± 591.8 SDM vs. control 1216.6 ± 854.4 [U/mL], p < 0.0001) and later after vaccination (324.1 ± 591.8 vs. 582.0 ± 415.6 [U/mL], p = 0.0002). The interval between vaccination of the RA patients and serum collection was longer than for controls early after vaccination (142.1 ± 31.6 vs. 98.3 ± 11.2 [days], p < 0.0001), but shorter than the later sample from the controls (142.1 ± 31.6 vs. 257.3 ± 11.2 [days], p < 0.0001). Importantly, anti-SARS-CoV-2 neutralizing Ab titers in RA patients were higher than in either early or later control samples (10.7 ± 4.9 vs. 8.6 ± 6.6 [%], p = 0.0072, and 10.7 ± 4.9 vs. 3.1 ± 3.7 [%], p < 0.0001, respectively). Anti-SARS-CoV-2 S Ab titers in vaccinated RA patients were lower than in controls, but they were influenced by other clinical manifestations. Anti-SARS-CoV-2 neutralizing Ab levels were independently increased in RA.

Waning of Anti-SARS-CoV-2 Spike Antibody Levels 100 to 200 Days after the Second Dose of the BNT162b2 Vaccine.

Anti-SARS-CoV-2 antibodies of 444 vaccinated hospital employees in Japan were measured 94-109 days and 199-212 days after receiving the second BNT162b2 vaccine dose to evaluate the intensity and duration of antibody response in our own cohort. Among uninfected participants, anti-S antibody levels were greatly decreased 199-212 days after the second vaccination compared to the levels measured 94-109 days after the second vaccination (median levels: 830 AU/mL and 2425 AU/mL, respectively; p < 0.001). The rate of decrease between the two testing periods was lower in infected participants than in uninfected participants (median: 47.7% and 33.9%, respectively; p < 0.001). Anti-S antibody levels were significantly higher in females (median: females, 2546 AU/mL; males, 2041 AU/mL; p = 0.002 during the first test period). The peak body temperature after vaccination was higher in females than in males (median: females, 37.4 °C; males: 37.1 °C; p = 0.044). Older males tended to have lower antibody levels. In conclusion, the duration of the anti-S antibody response to the BNT162b2 vaccine was short-lived, particularly in males. Anti-S antibody levels of 1000 AU/mL or lower according to SARS-CoV-2 IgG II Quant (Abbott) might indicate insufficient prevention against the delta variant, and the majority of participants appeared to have lost their protection 200 days after vaccination.

Humoral Responses After SARS-CoV-2 mRNA Vaccination and Breakthrough Infection in Cancer Patients.

OBJECTIVE: To evaluate the magnitude of humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with cancer receiving active therapies. PATIENTS AND METHODS: Patients 18 years or older in whom SARS-CoV-2 spike antibody (anti-S Ab) levels were measured after 2 doses of SARS-CoV-2 mRNA vaccines were included. Patients with prior coronavirus disease 2019 (COVID-19) infection or receiving other immunosuppressive therapy were excluded. RESULTS: Among 201 patients who met the criteria, 61 were immunocompetent, 91 had a hematologic malignancy, and 49 had a solid malignancy while receiving treatments associated with cytopenia, including chemotherapy or cyclin-dependent kinase 4 and 6 inhibitors. A significantly greater proportion of immunocompetent patients (96.7% [59 of 61]) had anti-S Ab titers of 500 U/mL or greater compared to patients with hematologic (7.7% [7 of 91) and solid (55.1% [27 of 49]) malignancy (P<.001). Despite 2 doses of SARS-CoV-2 mRNA vaccines, 52.7% of patients with hematologic malignancy (48 of 91) and 8.2% of those with solid malignancy (4 of 49) receiving cytopenic therapy had no seroconversion (spike antibody titers <0.8 U/mL). Two patients subsequently had development of breakthrough COVID-19 infection after full vaccination. CONCLUSION: A substantial proportion of patients with hematologic and solid malignancies receiving chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. Our study adds to a growing body of literature suggesting that immunosuppressed patients have a suboptimal humoral response to COVID-19 vaccination. Our study also underscores the importance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.

The Meaning of SARS-CoV-2 Antibodies in a Patient with a Systemic Reaction to the mRNA-1273 SARS-CoV-2 Vaccine after Previous Natural Immunization.

OBJECTIVES: There is limited experience regarding the meaning of SARS-CoV-2 antibodies after vaccination in patients with naturally acquired immunity. METHODS: We describe the case of a patient who received the first dose of the mRNA-1273 SARS-CoV-2 vaccine 6 months after his recovery from moderately severe COVID-19. RESULTS: Our patient had a positive nucleocapsid SARS-CoV-2 IgG/IgM titre with 78.7 multiple of cut-off indicating persistent humoral immune response 6 months after infection. After vaccination, he developed prolonged systemic symptoms (fever, fatigue, nausea, diarrhoea and myalgia) for a duration of 6 days. CONCLUSION: SARS-CoV-2 nucleocapsid antibodies provide information about naturally acquired immunity. For the assessment of immune response to vaccination, measurement of the SARS-CoV-2 spike antibody titre before and after vaccination is essential. Patients with naturally acquired immunity might develop a prolonged systemic reaction to the first dose of the mRNA-1273 SARS-CoV-2 vaccine. LEARNING POINTS: Patients with naturally acquired immunity might develop a prolonged systemic reaction after receiving an mRNA SARS-CoV-2 vaccine.Depending on the clinical situation of SARS-CoV-2 infection and/or vaccination, different antibody titres should be determined.The SARS-CoV-2 nucleocapsid antibodies provide information on whether or not natural immunization has taken place. To quantify the immune response induced by vaccination, the SARS-CoV-2 spike antibody titre before and after vaccination has to be measured.