Study suggests robust lung mucosal immunity against SARS-CoV-2 can be better achieved through hybrid immunity, as opposed to peripheral vaccination alone

In a recent study posted to the bioRxiv* preprint server, researchers characterized immunological responses by pulmonary mucosal tissues post-coronavirus disease 2019 (COVID-19) vaccination and/or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to assess the impact of hybrid immune protection on the durability of mucosal immunological responses.

Study: Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination. Image Credit: Kateryna Kon/Shutterstock
Study: Long-term respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination. Image Credit: Kateryna Kon/Shutterstock

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Previous studies have reported that COVID-19 vaccine-induced respiratory mucosal immune responses are essential for immunological protection against SARS-CoV-2. Serological anti-SARS-CoV-2 responses have been studied extensively among humans; however, the potential of peripheral COVID-19 vaccines in generating persistent cellular and humoral immunity in pulmonary mucosal tissues and the effects of prior COVID-19 history on peripheral immune responses is not known.

Improved knowledge of the longevity and breadth of adaptive immunological responses against SARS-CoV-2 in the human airways could enable utilizing mucosal immune responses in developing next-generation COVID-19 vaccines, which may prevent SARS-CoV-2 transmission and reduce COVID-19 case counts. The authors of the present study previously reported on the presence of cross-protective T lymphocytes in the human airways.

About the study

In the present study, researchers assessed the potential of peripheral COVID-19 vaccinations to elicit anti-SARS-CoV-2 immunological memory in human pulmonary mucosal tissues and investigated whether prior COVID-19 history influenced the immune outcomes.

BAL (bronchoalveolar lavage) fluid samples and matched serum samples were obtained from seven COVID-19 vaccine recipients without any prior COVID-29 history and 15 COVID-19 vaccinees infected with SARS-CoV-2 between two months and 11.0 months before COVID-19 vaccination. In addition, samples were obtained from 11 pre-pandemic control individuals with neither history of COVID-19 nor previous COVID-19 vaccination.  

The team assessed to evaluate the presence of mucosal and peripheral antibodies and anti-SARS-CoV-2 T lymphocytes and B lymphocyte responses. Immunoglobulin A (IgA) and IgG titers of mucosal and circulating antibodies against the SARS-CoV-2 S (spike) protein, against the RBD (receptor-binding domain), and the N (nucleocapsid) protein were determined. To detect anti-SARS-CoV-2 MBCs (memory B cells), fluorescently labeled spike, N, and RBD proteins were used for assaying peripheral blood mononuclear cells (PMBCs) and pulmonary leukocytes.

Results

The team observed humoral and cell-mediated immunity with enriched anti-spike protein titers, class-switched memory B lymphocytes, and T lymphocytes in pulmonary mucosal tissues than the peripheral titers in the background of hybrid immune responses. On the contrary, concerning COVID-19 vaccinations only, local-level anti-SARS-CoV-2 immune responses were restricted to humoral responses. Anti-S T lymphocytes were persistent in pulmonary mucosal tissues for ≤5.0 months after COVID-19 vaccination, and cross-reactive T lymphocyte responses were observed for ≥11 months post-SARS-CoV-2 infection.

In addition, a greater abundance of the cluster of differentiation 4+ (CD4+) and CD8+ T lymphocytes against SARS-CoV-2 were observed among SARS-CoV-2-exposed individuals than control individuals. Anti-nucleocapsid immunoglobulin G (IgG) titers were below/near the limit of sensitivity (LOS) among SARS-CoV-2 naïve COVID-29 vaccinees, whereas among SARS-CoV-2-infected individuals, the titers were detectable among serological samples of all 15 individuals, and among BAL samples of seven (47.0%) of individuals.

COVID-19 vaccinations induced robust systemic immunoglobulin G titers against spike protein and RBD, with three-fold greater titers among the infected and vaccinated individuals, in comparison to the SARS-CoV-2-naïve vaccinees.

Pulmonary anti-spike and anti-receptor-binding domain immunoglobulin G titers were eight-fold and nine-fold greater among individuals with hybrid immunity compared to the SARS-CoV-2-naïve vaccinees, respectively. Compared to control individuals, SARS-CoV-2-infected COVID-19 vaccinees showed three-fold higher mucosal IgA titers against the spike protein and higher greater IgA titers against SARS-CoV-2 RBD. Vaccination-elicited humoral responses in BAL and sera against SARS-CoV-2 S showed strong correlations for immunoglobulin G and lesser for immunoglobulin A.

Only COVID-19 vaccine recipients priorly exposed to SARS-CoV-2 N by infection showed detectable serological anti-N MBCs. The frequencies of MBCs against the spike protein, nucleocapsid protein, and receptor-binding domain were higher in pulmonary mucosal tissues of priorly infected COVID-19 vaccinees in comparison to pre-COVID-19 pandemic control individuals (median values of 6.0% versus 0.1% for the spike, 3.0% versus 0.1% for S RBD and 2.0% versus 0.2% for the N protein.

Paired sample comparisons of counts of mucosal and circulating anti-SARS-CoV-2anti-SARS-CoV-2 MBCs among infected vaccinees showed enriched anti-spike and anti-RBD memory B lymphocytes in the pulmonary mucosal tissues. Median counts of anti-spike and anti-S RBD memory B lymphocytes were two-fold and four-fold greater in BAL fluid samples than PMBCs. Additionally, the anti-SARS-CoV-2 CD4+ T lymphocytes and CD8+ T lymphocytes were greater in the lower airways compared to the peripheral vaccinations.

Conclusion

The study findings showed that durable pulmonary mucosal immune responses against SARS-CoV-2 could be observed post-hybrid immunity development and cannot be induced by peripheral COVID-19 vaccinations only. Long-term, airway-compartmentalized B lymphocyte and T lymphocyte pulmonary reservoirs might confer enhanced identification of SARS-CoV-2 Omicron subvariants and future variants to prevent COVID-19 severity outcomes. Therefore, the findings underscored the development of COVID-19 vaccines targeting human airways.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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Comments

  1. Curtis Brookover Curtis Brookover United States says:

    Zero clot shot is the control group.  Such ridiculous research.  You need to be infected for long term immunity, duh.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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