Exploring Plasma and Nasal Antibody Responses to SARS-CoV-2 Infection and Vaccination

Exploring Plasma and Nasal Antibody Responses to SARS-CoV-2 Infection and Vaccination

In a recent study published in eBioMedicineresearchers assessed plasma and nasal antibody titer responses induced by natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccination against coronavirus 2019 (COVID-19) in subjects residents of the United Kingdom (UK).

Exploring Plasma and Nasal Antibody Responses to SARS-CoV-2 Infection and Vaccination
Study: Nasal IgA specific for SARS-CoV-2 declines 9 months after hospitalization with COVID-19 and is not induced by subsequent vaccination. Image credit: CKA/Shutterstock

Anti-SARS-CoV-2 systemic immunity is essential for the prevention of COVID-19 disease; however, mucosal immune responses prevent SARS-CoV-2 proliferation at the host point of entry and, therefore, reduce onward transmission of SARS-CoV-2. However, data on mucosal defense against SARS-CoV-2 are limited and merit further investigation.

About the study

In the present study, researchers reported serological and mucosal immune responses to SARS-CoV-2 after one year of SARS-CoV-2 infection.

Nasal and plasma specimens were prospectively obtained from 446 adult PHOSP-COVID and ISARIC4C (Severe and Emerging Acute Respiratory Infections Consortium) adult participants hospitalized with SARS-CoV-2 infection between February 2020 and March of the following year. Additionally, specimens were obtained from healthy individuals with no history of lung disease. Specimens were obtained during the first nine days of hospitalization and every 1.0 to 14.0 months after hospital discharge.

Samples were also obtained semi-annually and annually between November 2020 and March 2022, which is for the duration of the initial rollout of the COVID-19 vaccine in the UK. Where missing, COVID-19 vaccination data was extracted from the outbreak data analysis platform (ODAP). The severity of COVID-19 was assessed based on World Health Organization (WHO) clinical progression scores.

Immunoglobulin G (IgG) and IgA titers against the nucleocapsid (NP) protein and receptor-binding domain (RBD) of the spike (S) protein of the ancestral strain of SARS-CoV-2 , Delta variant and Omicron variant were determined using multiplexed electrochemiluminescence assays. Serological results and SARS-CoV-2 neutralization results were evaluated comparatively. Additionally, the ratio of anti-RBD antibodies for the Omicron variant and the ancestral strain was determined to assess the extent of cross-reactivity. Additionally, the PubMed database was searched using terms such as “nasal”, “mucosal”, “IgA”, “antibody”, SARS-CoV-2, COVID-19, “vaccination and “recovering” to find relevant reports written in English and published before July 20, 2022.


Robust nasal IgA titers against SARS-CoV-2 proteins S and NP were observed, which remained elevated for 9.0 months. In contrast, plasma and nasal IgG titers against SARS-CoV-2 S remained elevated ≥1.0 yr, with plasma IgG titers elevated against all SARS-CoV-2 variants (less for Omicron ) compared to controls. Between 6.0 months and one year, 307 people were vaccinated, coinciding with an increase in plasma and nasal immunoglobulin A and immunoglobulin G titers against SARS-CoV-2 protein S of all variants tested, even if the titers of nasal anti-S IgA were multiplied by only 1.5.

Nasal antibodies induced by pre-Omicron variant infections bound to Omicron variant S protein. in vitro better than plasma antibodies. Nasal IgA titers decreased and were only minimally boosted by vaccination, while plasma anti-S titers were constant and boosted by COVID-19 vaccination. SARS-CoV-2 S IgG titers were observed within 2 weeks of onset of COVID-19 symptoms and increased 2181-fold after nine months. Unlike IgA titers, they persisted above pre-pandemic levels.

Anti-NP IgG and IgA titers remained low after nine months. While nasal anti-S titers peaked between six and nine months, and anti-NP titers between three and five months, plasma titers peaked 28 days before declining. Serological titers against SARS-CoV-2 NP remained constant after 10.0 months. Only two patients showed serological evidence of reinfection (high IgG titers against SARS-CoV-2 S and NP proteins) after infection. After vaccination, nasal IgA titers against SARS-CoV-2 protein S increased transiently, whereas no difference was observed between anti-NP and anti-S titer trajectories.

In contrast, anti-S nasal IgG titers increased significantly and reached a peak 100 days after vaccination. Further analysis indicated that vaccinations may not completely evoke mucosal immunoglobulin A antibody responses. Nasal IgG and IgA titers against RBD Omicron and RBD Delta were observed within four weeks of symptom onset and persisted at elevated levels for ≥9.0 months.

Pre-Omicron variant infections could induce plasma and nasal antibodies binding to Omicron RBD, which showed greater cross-reactivity. COVID-19 vaccines boosted plasma and nasal Delta-binding and Omicron-binding IgG titers, but to a lesser extent than ancestral strain titers. In contrast, nasal IgA titers binding to Delta and Omicron were not significantly affected by COVID-19 vaccination. Plasma neutralizing antibodies were correlated with anti-S and anti-RBD nasal IgG titers, but not nasal IgA titers.

A compartmentalization of nasal IgA titers versus plasma titers was observed with the formation of four clusters, resulting from the temporary increase in nasal immunoglobulin A titers after the recent COVID-19 vaccination, with a divergence between the plasma and nasal IgA titers with increasing time since vaccination. Group 1 included patients with elevated plasma and nasal IgA titers. Individuals with the lowest plasma IgG and IgA titers constituted the second group, while those with the lowest nasal IgA titers were included in the third and fourth groups.

Three relevant studies from the PubMed database were identified which reported persistence of nasal antibodies for three months to nine months and also an increase in nasal IgG and IgA 7.0 days to 10 days after vaccination. Durable plasma and nasal IgG titers against all strains tested were elevated by intramuscular vaccinations. However, the sample sizes were small and mostly included people with mild SARS-CoV-2 infection.

Overall, study results showed a drop in nasal IgA titers 9.0 months post-infection, which were only minimally increased by COVID-19 vaccination, explaining the absence of a long-term protective nasal defense against pernicious infections. A distinct compartmentalization between serum IgA titers and nasal IgG and IgA titers was observed after vaccination. These results highlight the need to develop vaccines that boost nasal immunity and booster doses to achieve long-lasting cross-immune responses.

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