BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection? (original) (raw)
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Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA
Frontiers in Immunology, 2023
We revealed strong mucosal neutralization upon BNT162b2 vaccination, mediated by temporary polymeric IgA, and explored its longitudinal properties. We describe immunological characteristics and kinetics of the IgG and IgA response and of its mucosal component upon mRNA vaccination with BNT162b2. We suggest a methodology for quantitative comparison of immunoreactivity and neutralization for IgG and IgA in serum and saliva in molar equivalents that may apply for standardization in diagnostics, for surveillance of protection, and for vaccine evaluations. 126. Fuerst TR, Niles EG, Studier FW, Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase.
Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces robust neutralizing salivary IgA
2022
Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable ‘sterilizing immunity’ at the mucosal level. Our study uncovers, strong neutralizing mucosal component (NT50 ≤ 50pM), emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the Receptor-Binding-Domain (RBD) of SARS-CoV-2 spike protein and demonstrate that these IgAs are key mediators of potent neutralization. RBD-targeting IgAs were found to associate with the Secretory Component, indicating their bona-fide transcytotic origin and their dimeric tetravalent nature. The mechanistic understanding of the exceptionally high neutralizing activity provided by mucosal IgA, acting at the first line of defence, will advance vaccination design and surveillance principles, pointing to novel treatment approaches, and to new routes of vaccine administration and boosting.S...
Mucosal Immunology
Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccineinduced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection.
Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in saliva
2021
Vaccines are critical for curtailing the COVID-19 pandemic (1, 2). In the USA, two highly protective mRNA vaccines are available: BNT162b2 from Pfizer/BioNTech and mRNA-1273 from Moderna (3, 4). These vaccines induce antibodies to the SARS-CoV-2 S-protein, including neutralizing antibodies (NAbs) predominantly directed against the Receptor Binding Domain (RBD) (1-4). Serum NAbs are induced at modest levels within ∼1 week of the first dose, but their titers are strongly boosted by a second dose at 3 (BNT162b2) or 4 weeks (mRNA-1273) (3, 4). SARS-CoV-2 is most commonly transmitted nasally or orally and infects cells in the mucosae of the respiratory and to some extent also the gastrointestinal tract (5). Although serum NAbs may be a correlate of protection against COVID-19, mucosal antibodies might directly prevent or limit virus acquisition by the nasal, oral and conjunctival routes (5). Whether the mRNA vaccines induce mucosal immunity has not been studied. Here, we report that anti...
Vaccines
SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic. Approved mRNA COVID-19 vaccines are well known to induce a serum antibody responses against the spike protein and its RBD. Mucosal immunity plays a major role in the fight against COVID-19 directly at the site of virus entry; however, vaccine abilities to elicit mucosal immune responses have not been reported. We detected anti-SARS-CoV-2 IgA-S1 and IgG-RBD in three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection) on serum, saliva, and nasal secretions using two commercial immunoassays (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD). Our results show that the mRNA BNT162b2 vaccine Comirnaty (Pfizer/BioNTech, New York, NY, USA) determines the production of nasal and salivary IgA-S1 and IgG-RBD against SARS-CoV-2. This mucosal humoral immune response is stronger after the injection of the second vaccine dose compared to subjects recovered from COV...
2021
ABSTRACTBackgroundImmunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves the oral cavity, a primary site of infection, is presently unknown.MethodsImmunocompromised individuals (n=404) and healthy controls (n=82) participated in a prospective clinical trial encompassing two doses of the mRNA BNT162b2 vaccine. Immunocompromised individuals included primary immunodeficiencies (PID) and secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL). Saliva and serum samples were collected at four time points from the first vaccine dose until 2 weeks after second dose. SARS-CoV-2 spike specific immunoglobulin G (IgG) responses were quantified by a multi...
Frontiers in Immunology, 2021
SARS-CoV-2 antibodies in saliva serve as first line of defense against the virus. They are present in the mucosa, more precisely in saliva, after a recovered infection and also following vaccination. We report here the antibody persistence in plasma and in saliva up to 15 months after mild COVID-19. The IgG antibody response was measured every two months in 72 participants using an established and validated in-house ELISA assay. In addition, the virus inhibitory activity of plasma antibodies was assessed in a surrogate virus neutralization test before and after vaccination. SARS-CoV-2-specific antibody concentrations remained stable in plasma and saliva and the response was strongly boosted after one dose COVID-19 vaccination.
SARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals
Nature Communications
Immune responses at the respiratory mucosal interface are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. Here we analyze paired serum and saliva samples from patients with and without prior coronavirus disease 2019 (COVID-19) at multiple time points pre and post severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest mucosal SIgA responses induced by mRNA vaccination are impacted by pre-existing immunity. Indeed, vaccination induced a minimal mucosal SIgA response in individuals without pre-exposure to SARS-CoV-2 while SIgA induction after vaccination was more efficient in patients with a history of COVID-19.
SSRN Electronic Journal
Background Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses. Methods Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS). Findings Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigenexperienced ones. All vaccinees had increased galactosylated and sialylated anti-S IgG1. Both naive and antigen