IgA dominates the early neutralizing antibody response to SARS-CoV-2
diagnostics immunology/immunity therapeutics vaccines
Authors: Sterlin et al.
Journal/ Pre-Print: medRxiv
Tags: Diagnostics; Immunology/Immunity; Therapeutics; Vaccines
Longitudinal analysis of phenotypic changes in B cells and their antibody secretion
Photonic ring immunoassay to test purified antibodies against various viral antigens revealed potent IgA neutralisation targeting the RBD region of SARS-CoV-2
Early SARS-CoV-2-specific humoral responses are dominated by IgA-producing plasmablasts, but IgG antibody titers are prevalent in the serum at later stages
Sterlin et al aimed to characterise the humoral immune response following SARS-CoV-2 infection. They performed a longitudinal serum analysis in 38 infected patients with differing severities of COVID-19 disease course. Phenotyping the immune compartment revealed a majority of CCR10-expressing plasmablast at the onset of disease. The early humoral response is dominated by IgA-secreting plasmablasts, whose antibodies were more efficient at neutralising SARS-CoV-2. Late stages of COVID-19 revealed a predominance of IgG in the serum. They also assessed local immunity using bronchoalveolar lavage (BAL) of severe patients harvested at different timepoints, which showed a predominance of IgG. Therefore, mucosal and systemic response against SARS-CoV-2 may differ and needs to be taken into account regarding vaccine design and antibody tests.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19: analysing the humoral immune response over time
Develop a vaccine for SARS-CoV-2: looking at humoral antibody responses over time is important for shaping vaccine design
Patient Case study
Strengths and limitations of the paper
Novelty: Longitudinal phenotyping of humoral response including B cells, Tfh and antibody responses; testing antibodies in serum for neutralising activity, IgA antibodies have greater neutralising potential
Standing in the field: IgA responses suggested as early biomarker in several studies, contradicts another study regarding Tfh cell numbers over time
Appropriate statistics:Statistics seem appropriate to our knowledge and are described in methods.
Viral model used: Original SARS-CoV-2 infected patients, pseudovirus used for neutralisation assays
Translatability: Assessing humoral response and its protectivity over time is important for successful vaccine design, potential application for antibody test design
Main limitations: Limitations described in discussion, antibody responses not stratified based on severity of COVID-19 infection, BAL samples obtained only from severe patients, longitudinal studies should compare various sites (mucosal vs systemic), IgG antibodies protectivity wasn’t assessed in healthy donors