A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients

Abstract

BackgroundMucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine.MethodsTwenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism.ResultsIn COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine dosesConclusionThis study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.

Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission

“…Unaccountably omitted from consideration is the possibility that prior SARS-CoV-2 infection had primed mucosal immune responses that were recalled by the subsequent systemic vaccination, as noted above ( 14 ). Evidence for this is now forthcoming from a report that systemic vaccination (one dose) of previously infected subjects induced the appearance in peripheral blood of IgA anti-spike antibody-secreting cells with mucosal homing potential approximately one week after immunization, as well as IgA antibodies in nasal fluids ( 15 , reviewed by 80 ), in conformity with the known operation of the mucosal immune system ( 81 ). In previously uninfected subjects, IgA antibody-secreting cells of mucosal phenotype were absent from the circulation and nasal IgA antibodies were not induced, even after a second vaccine dose.…”

“…In contrast, mucosal immunization induces mucosal responses but not parallel systemic immune responses, thereby demonstrating a considerable degree of mutual independence ( 11 – 13 ). However, antigens previously introduced by a mucosal route can also prime the immune system so that subsequent systemic immunization induces both systemic and mucosal antibody responses ( 14 , 15 ). There are several examples of the effectiveness of systemic immunization of individuals who were previously exposed to a particular antigen at a mucosal surface for the generation of mucosal responses.…”

Multiplex Hybrid Antigen-Capture LC-MRM Quantification in Sera and Nasal Lining Fluid of AZD7442, a SARS-CoV-2-Targeting Antibody Combination

“…10 The sensitivity of the bead-based antibody assays varied by analyte with the lower limit of quantification [LLOQ] for interleukin [IL]-5 being 0.27 pg/mL 41 and the lower limit of detection [LLOD] being 2.0 pg/mL for IL-5. 40 For the serological assays the reported LLODs were in the range 0.44−11.00 binding antibody units (BAU/mL), 42 while for the electro-chemiluminescent assays the reported total protein levels were only in the μg/mL range. 38 To our knowledge, only one LC-MS/MS method related to protein profiling in NLF has been reported in peerreviewed publications to date.…”

“…Common methods for mAb bioanalysis in NLF consist of ELISA, 10,35−37 electrochemiluminescence, 38,39 bead-based antibody assays, 40,41 and other commercially available serological assays. 42 Generally, the ELISA assays were semiquantitative, 36,37 intended for research purposes only (with manufacturer reported range of 250− 16,000 pg/mL), 35 or reported standard curve in the ng/mL range (0.195−200 ng/mL). 10 The sensitivity of the bead-based antibody assays varied by analyte with the lower limit of quantification [LLOQ] for interleukin [IL]-5 being 0.27 pg/mL 41 and the lower limit of detection [LLOD] being 2.0 pg/mL for IL-5.…”

“…Similarly, a highly sensitive LBA-LC-MS/MSbased assay was developed and qualified for the absolute quantification of the two mAbs in human NLF. NLF is a hitherto under-evaluated matrix gaining interest as a patientcentric matrix in studies of COVID-19, 2,37,42,48 and other respiratory diseases. 49−52 This approach highlights the importance of mature technology, and an appropriate development strategy to enable the fast deployment of a high-quality PK assay that allowed for the rapid evaluation of AZD7442 during a global COVID-19 pandemic.…”