Month: November 2024

Jian-Piao Cai: Writing C review & editing, Methodology, Data curation. of prior infection status. Among non-infected individuals, serum IgG, serum IgA and salivary IgG levels were significantly higher against the ancestral strain than the Omicron BA.2 sublineage, but salivary IgA levels PF-04929113 (SNX-5422) did not differ between the strains. Salivary IgA had the weakest correlation with serum IgG (r?=?0.34) compared with salivary IgG (r?=?0.63) and serum IgA (r?=?0.60). Our findings suggest that intramuscular COVID-19 vaccines elicit a distinct mucosal IgA response that differs from the systemic IgG response. As mucosal IgA independently correlates with protection, vaccine trials should include mucosal IgA as an outcome measure. Keywords: COVID-19 vaccine, SARS-CoV-2, Omicron variant, Mucosal immunity, Saliva, IgA 1.?Introduction SARS-CoV-2 has emerged in 2019 and caused the COVID-19 pandemic. The World Health Organization estimated that COVID-19 was associated with 14. 83 million excess deaths globally from January 2020 to December 2021 [1]. COVID-19 is also associated with a higher risk of 30-day mortality and hospital readmission when compared with influenza [2]. SARS-CoV-2 has evolved into different variants. The Omicron variant, which escape immunity induced by prior infection or vaccination, emerged in late 2021 and led to major outbreaks [3]. Humoral immunity plays an important role in the protection against SARS-CoV-2 infection. Higher levels of systemic (serum or plasma) neutralizing antibodies or SARS-CoV-2-spike-protein-specific (S-specific) IgG correlate with a better vaccine effectiveness against symptomatic infection and a lower risk of reinfection [[4], [5], [6]]. Omicron variant, which emerged in late 2021 and escaped neutralization by systemic antibodies elicited from prior infection or vaccination [[7], [8], PF-04929113 (SNX-5422) [9], [10]], was associated with poorer vaccine effectiveness [11]. Hence, systemic IgG or neutralizing antibodies have been considered to be a major correlate of protection, and have been used as the outcome measure in Rabbit Polyclonal to PKCB COVID-19 vaccine trials [12]. SARS-CoV-2 primarily infects and replicates in the respiratory tract, making mucosal immunity a crucial first line of defence against the virus. Secretory immunoglobulin PF-04929113 (SNX-5422) A (IgA), derived from subepithelial plasma cells, is the major player of the respiratory tract immunity. During an acute SARS-CoV-2 infection or after COVID-19 vaccine, the level of S-specific IgA increases rapidly in the saliva [13,14]. S-specific dimeric IgA, the form present on mucosal surface, exhibits a stronger neutralizing activity than plasma monomeric IgA [15]. Several studies demonstrated that higher levels of salivary or nasal mucosal IgA correlate with lower nasopharyngeal viral load or protection from vaccine breakthrough infection [14,[16], [17], [18]], and the protection is independent from the level of systemic antibodies. While numerous studies have reported that the levels of systemic neutralizing antibodies and S-specific IgG can be affected by vaccine type and booster doses [4,6,7], only a few have examined the levels of S-specific mucosal IgA after intramuscular COVID-19 vaccines [[19], [20], [21]]. The primary aim of the current study was to compare the levels of mucosal and systemic antibodies induced by the mRNA vaccine BNT162b2 and the inactivated whole virion vaccine CoronaVac, and to determine the impact of booster doses. We observed no significant difference in the mucosal PF-04929113 (SNX-5422) IgA response between CoronaVac and BNT162b2 in stark contrast to the differences observed in mucosal IgG, serum IgA, and serum IgG responses. We also found that mucosal IgA has a broader binding capacity than other serum or salivary antibodies. 2.?Materials and methods 2.1. Study design and study participants This was a cross-sectional study that followed the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. We recruited adult patients who attended the medical out-patient clinic of Queen Mary Hospital in Hong Kong between 20 June and September 8, 2022, after the Omicron BA.2 wave. Patients were eligible for inclusion if they were aged 18 years or above, and received at least 2 doses of BNT162b2 or CoronaVac. Exclusion criteria included the receipt of both BNT162b2 and CoronaVac, refusal to provide written informed consent, mental incapacity to provide written informed consent, or unable to provide sufficient volume of saliva or blood (Fig. 1.). Open in a separate window Fig. 1 STROBE flow diagram of the study. On the day of recruitment, we collected blood and saliva specimens for testing of IgA and IgG PF-04929113 (SNX-5422) against the SARS-CoV-2 spike protein receptor binding domain (RBD). We obtained data on vaccination history and COVID-19 infection history. Study participants were classified as having prior infection with SARS-CoV-2 if they had known positive RT-PCR or rapid antigen test results. For patients who have not received inactivated whole virion vaccine, they were also considered to have prior infection if their anti-nucleoprotein IgG (anti-N IgG) was positive. 2.2. Collection and processing of saliva specimens Saliva specimens were collected using Salivette? (Sarstedt) according.