Systemic and Mucosal Humoral Immune Response Induced by Three Doses of the BNT162b2 SARS-CoV-2 mRNA Vaccines

Mancuso, Roberta; Agostini, Simone; Citterio, Lorenzo Agostino; Chiarini, Debora; Santangelo, Maria Antonia; Clerici, Mario

doi:10.3390/vaccines10101649

Cited by 4 publications

(2 citation statements)

References 66 publications

(77 reference statements)

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“…Several studies have reported detectable increases in saliva IgA after initial and/or booster vaccination with COVID-19 mRNA vaccines. 24,[26][27][28][29]46 Others, more consistent with our findings, have observed only minimal IgA responses in uninfected individuals. 25,30,31 A potential limitation of COVID-19 vaccine studies is possible inclusion of individuals with prior subclinical infections, as vaccination after prior SARS-CoV-2 infection can induce significant saliva anti-SCV2 spike IgA responses.…”

Section: Discussionsupporting

confidence: 92%

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses

Conner,

Goguet,

Haines-Hull

et al. 2024

Preprint

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This study characterized antibody responses induced by COVID-19 mRNA vaccination and SARS-CoV-2 infection in saliva. Utilizing multiplex microsphere-based immunoassays, we measured saliva anti-SARS-CoV-2 spike IgG, IgA, and secretory IgA in 1,224 saliva samples collected from healthcare workers in the Prospective Assessment of SARS-CoV-2 Seroconversion study between August of 2020 through December of 2022. By spring of 2022, most individuals had detectable spike-specific antibodies in saliva. Longitudinal measurements of saliva anti-SARS-CoV-2 nucleocapsid IgG revealed that most spike-specific IgA and secretory IgA detected in saliva was driven by subclinical and clinically-evident infections, rather than by vaccination alone. In contrast, saliva anti-SARS-CoV-2 spike IgG was strongly induced by vaccination and exhibited improved durability with hybrid immunity. Baseline levels of saliva antibodies to the endemic human coronaviruses positively correlated with post-vaccination anti-SARS-CoV-2 spike IgG levels. This study provides insights for development of vaccines that generate mucosal antibodies to respiratory pathogens.

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Section: Discussionsupporting

confidence: 92%

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses

Conner,

Goguet,

Haines-Hull

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…However, they reported higher levels of IFN-α in nasal washes from symptomatic COVID-19 patients [ 18 ]. Compartmentalization of Ab responses has also been described in convalescent individuals [ 19 , 20 ] and following immunization with the BioNTech/Pfizer vaccine [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen

et al. 2023

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The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-β. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.

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Robust memory humoral immune response to SARS-CoV-2 in the tonsils of adults and children

Altorki,

Abdulal,

Suliman

et al. 2023

Front. Immunol.

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BackgroundAdaptive humoral immunity against SARS-CoV-2 has mainly been evaluated in peripheral blood. Human secondary lymphoid tissues (such as tonsils) contain large numbers of plasma cells that secrete immunoglobulins at mucosal sites. Yet, the role of mucosal memory immunity induced by vaccines or natural infection against SARS-CoV-2 and its variants is not fully understood.MethodsTonsillar mononuclear cells (TMNCs) from adults (n=10) and children (n=11) were isolated and stimulated using positive SARS-CoV-2 nasal swabs. We used endpoint enzyme-linked immunosorbent assays (ELISAs) for the measurement of anti-S1, -RBD, and -N IgG antibody levels and a pseudovirus microneutralization assay to assess neutralizing antibodies (nAbs) in paired serum and supernatants from stimulated TMNCs.ResultsStrong systemic humoral response in previously SARS-CoV-2 infected and vaccinated adults and children was observed in accordance with the reported history of the participants. Interestingly, we found a significant increase in anti-RBD IgG (305 and 834 folds) and anti-S1 IgG (475 and 443 folds) in the stimulated TMNCs from adults and children, respectively, compared to unstimulated cells. Consistently, the stimulated TMNCs secreted higher levels of nAbs against the ancestral Wuhan strain and the Omicron BA.1 variant compared to unstimulated cells by several folds. This increase was seen in all participants including children with no known history of infection, suggesting that these participants might have been previously exposed to SARS-CoV-2 and that not all asymptomatic cases necessarily could be detected by serum antibodies. Furthermore, nAb levels against both strains were significantly correlated in adults (r=0.8788; p = 0.0008) and children (r = 0.7521; p = 0.0076), and they strongly correlated with S1 and RBD-specific IgG antibodies.ConclusionOur results provide evidence for persistent mucosal humoral memory in tonsils from previously infected and/or vaccinated adults and children against recent and old variants upon re-exposure. They also highlight the importance of targeting mucosal sites with vaccines to help control infection at the primary sites and prevent potential breakthrough infections.

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Systemic and Mucosal Humoral Immune Response Induced by Three Doses of the BNT162b2 SARS-CoV-2 mRNA Vaccines

Cited by 4 publications

References 66 publications

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses

Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen

Robust memory humoral immune response to SARS-CoV-2 in the tonsils of adults and children

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