Predictors for reactogenicity and humoral immunity to SARS-CoV-2 following infection and mRNA vaccination: A regularized, mixed-effects modelling approach.

Introduction: The influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood. Methods: Ten-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced by COVID+ participants during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses to recombinant spike protein in a longitudinal cohort study. Results: In previously infected individuals (n=33), AB were more durable and robust following primary vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose (n=49 and 48, respectively) of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination, suggesting that vaccination in COVID+ individuals is associated with a more robust immune response. Discussion: Experiencing systemic and local symptoms post-vaccine was suggestive of higher AB, which may confer greater protection.

Effect of FcRn antagonism on protective antibodies and to vaccines in IgG-mediated autoimmune diseases pemphigus and generalised myasthenia gravis.

Antagonism of the neonatal Fc receptor (FcRn) by efgartigimod has been studied in several autoimmune diseases mediated by immunoglobulin G (IgG) as a therapeutic approach to remove pathogenic IgGs. Whereas reduction of pathogenic titres has demonstrated efficacy in multiple autoimmune diseases, reducing total IgG could potentially increase infection risk in patients receiving FcRn antagonists. The objective of this study was to analyse the effect of FcRn antagonism with efgartigimod on existing protective antibody titres and the ability to mount an immune response after vaccine challenge. Serum levels of total IgG and protective antibodies against tetanus toxoid (TT), varicella zoster virus (VZV), and pneumococcal capsular polysaccharide (PCP) were measured in all patients enrolled in an open-label trial of efgartigimod for the treatment of pemphigus. Vaccine specific-responses were assessed by measuring changes in IgG titres in patients with generalised myasthenia gravis (gMG) who were treated with efgartigimod and who received influenza, pneumococcal, or coronavirus disease 2019 (COVID-19) vaccines during participation in the double-blind trial ADAPT or open-label extension, ADAPT+ (n = 17). FcRn antagonism reduced levels of protective anti-TT, anti-VZV, and anti-PCP antibodies and total IgG to a similar extent; anti-TT and anti-VZV titres remained above minimally protective thresholds for the majority of patients, (10/12) 83% and (14/15) 93% respectively. Protective antibodies returned to baseline values upon treatment cessation. Antigen-specific IgG responses to influenza, pneumococcal, and COVID-19 immunisation were detected in patients with gMG who received these vaccines while undergoing therapy with efgartigimod. In conclusion, FcRn antagonism with efgartigimod did not hamper generation of IgG responses but did transiently reduce IgG titres of all specificities.

Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant.

OBJECTIVES: The aim of the present study was to evaluate if neutralizing antibody responses induced by infection with the SARS-CoV-2 strain that was dominant at the beginning of the pandemic or by the Gamma variant was effective against the Omicron variant. METHODS: Convalescent sera from 109 individuals, never exposed to a SARS-CoV-2 vaccine, who had mild or moderate symptoms not requiring hospitalization following either a documented SARS-CoV-2 ancestral strain infection or a Gamma variant infection, were assayed for in vitro neutralizing antibody activity against their original strains and the Omicron variant. RESULTS: Following an infection with the ancestral strain, 56 (93.3%), 45 (77.6%) and 1 (1.7%) serum sample were positive for neutralizing antibodies against the ancestral, Gamma variant, and Omicron variant, respectively. After infection with the Gamma variant, 43 (87.8%) and 2 (4.1%) sera were positive for neutralizing antibodies against the Gamma and Omicron variants, respectively. CONCLUSIONS: Neutralizing antibodies generated following mild or moderate infection with the SARS-CoV-2 ancestral strain or the Gamma variant are not protective against the Omicron variant.

Stabilized coronavirus spike stem elicits a broadly protective antibody.

Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive ß-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies.

Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse. CASE PRESENTATION: We report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded. CONCLUSION: COVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.