BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)a biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-Gastroenterology 2021;-:1-14 CLINICAL ATspike antibody levels and functional activity, anti-TNFa levels and adverse events (AEs) were detected longitudinally. RE-SULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFa, 118 non-anti-TNFa), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas w7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFa treated compared with non-anti-TNFa treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFa treated compared with non-anti-TNFa treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFa drug levels and vaccine responses did not affect anti-spike levels. Infection rate (w2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFa, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

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The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.

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The importance of breastmilk in postnatal life lies in the strong association between breastfeeding and the reduction in the risk of infection and infection-related infant mortality. However, data regarding the induction and dynamics of breastmilk antibodies following administration of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine is scarce, as pregnant and lactating women were not included in the initial vaccine clinical trials. Here, we investigate the dynamics of the vaccine-specific antibody response in breastmilk and serum in a prospective cohort of ten lactating women who received two doses of the mRNA vaccine. We show that the antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose. The response in breastmilk includes both IgG and IgA with neutralization capacity.