Vaccines that induce mucosal immunity against SARS-CoV-2 are needed

In a recent study posted on medrex sib*Preprint server, UK researchers assessed plasma and nasal antibody (Ab) responses induced one year after hospitalization associated with coronavirus disease 2019 (COVID-19) and subsequent severe acute respiratory studied a potential boost by Syndrome Coronavirus 2 (SARS- CoV-2) vaccination (UK).

study: Nasal IgA decreases 9 months after hospitalization for COVID-19 and is not induced by subsequent vaccinationImage Credit: BINK0NTAN / Shutterstock

Studies have reported that a mucosal immune response prevents replication of SARS-CoV-2 at the point of entry and reduces subsequent viral infection. However, data on the correlation between mucosal humoral immunity and systemic immune responses during COVID-19 convalescence are limited. In addition, studies have been reported on enhanced immune responses after vaccination. However, whether the immune enhancement is due to passive translocation of plasma Abs to the mucosa or whether COVID-19 vaccination can recall mucosal responses primed by SARS-CoV-2 infection remains to be investigated further. is required.

Over time, SARS-CoV-2 has evolved with the emergence of multiple variants of concern (VOCs) with higher transmissibility and immune evasion. In particular, Omicron variants and subvariants have been shown to be less susceptible to vaccination-induced immune responses. The immunity generated as a combined effect of SARS-CoV-2 infection and vaccination may enhance immune combat against Omicron and other VOCs.

About research

In the current multicenter longitudinal study, researchers evaluated the persistence of mucosal immune responses to severe COVID-19 and the additional benefit of subsequent COVID-19 vaccination.

Clinical information, plasma, and nasal samples were collected from COVID-19 adult patients (n=446) hospitalized between February 2020 and March 2021 for PHOSP-COVID and ISARIC4C (International Severe Acute Respiratory and Emerging Infectious Diseases Consortium 4C) Prospectively acquired from the Consortium. Samples were obtained during the 9-day hospital stay and/or at convalescent intervals (1 to 14 months after discharge).

Samples obtained at 6 and 12 months post-vaccination from September 2020 to March 2022 cover the start of the UK COVID-19 vaccination campaign and the severity of COVID-19 globally. Classification was based on the Health Organization (WHO) Clinical Progression Score. Immunoglobulin G (IgG) and IgA titers against the SARS-CoV-2 nucleocapsid (NP), spike (S) protein of ancestral SARS-CoV-2 strains, delta and omicron BA.1 VOCs were measured by electrochemiluminescence. assessed by analysis.

Findings correlated with those of pseudotype neutralization assays performed on plasma samples. In addition, using search terms such as “nose”, “mucosa”, “IgA”, “antibodies”, “SARS-CoV-2”, “COVID-19”, “vaccination”, “recovery”, We searched the PubMed database. For related studies published in English before 20 July 2022.

As a result, three studies on the longevity of nasal antibody responses were analyzed and showed that nasal antibodies persisted for 3–9 months. However, the study included patients with mild SARS-CoV-2 infection and a small sample size. In addition, a study conducted in home caregivers (n=107) showed elevated salivary IgG titers after two mRNA (messenger ribonucleic acid) vaccinations, whereas another study An increase in nasal IgG and IgA titers was shown after 7-10 days of vaccination against SARS. – A person exposed to CoV-2.

result

In total, 569 and 356 plasma and nasal samples were obtained, of which 338 and 143, respectively, were obtained from the same person at different time intervals, and paired nasal and plasma samples obtained at the same time point were available for 174 individuals. did. Robust nasal anti-NP and anti-S IgA antibody titers were seen in him within 4 weeks of symptom onset and waned after 9 months.

Nasal IgA (A), nasal IgG (B), plasma IgA (C), and plasma IgG (D) responses to S from ancestral SARS-CoV-2, 12 months after onset, pre-pandemic controls Comparison with sample (grey). Nasal IgA (E), nasal IgG (F), plasma IgA (G), and plasma IgG (H) responses to ancestral SARS-CoV-2 NPs, 12 months after symptom onset. , compared with the pre-pandemic control sample. Blue and red lines indicate the median titer trajectory at each time point. The horizontal dashed line indicates the WHO threshold for seropositivity. titer* = p<0.05, ** = p<0.01, *** = p<0.001, **** = p<0.0001.​​​​​​​

Conversely, nasal and plasma anti-S IgG titers that appeared within 2 weeks of symptom onset were persistently elevated for more than 1 year, demonstrating plasma neutralization potency against all tested VOCs after 9 months of vaccination. was 2181 times higher. His nasal IgG and IgA anti-S titers increased after 10 months. However, only a 1.5-fold median change was observed for IgA only, and anti-NP IgG and IgA responses persisted at low levels after 9 months.

Two individuals developed reinfection (elevated anti-S and anti-NP IgG titers). In addition, 33 individuals with known vaccination status and pre- and post-vaccination samples had increased anti-S titers and decreased anti-NP titers. Most participants were vaccinated from 6 months to 1 year after vaccination, which is consistent with increases in plasma and nasal IgG and IgA anti-S titers to all VOCs. However, nasal IgA titers were slightly altered.

In samples obtained 1 year after admission, no association was found between plasma IgG and nasal IgA titers, and nasal IgA humoral responses, unlike plasma responses, were minimized by vaccination. was shown to be enhanced to A decrease in nasal IgA titers 9 months after natural SARS-CoV-2 infection and a minor effect of COVID-19 vaccination may be associated with a lack of long-term nasal mucosal protection against SARS-CoV-2 reinfection. and effects of vaccination on minimal viral infection. Infection-induced nasal antibody titers of circulating VOCs before Omicron showed binding to his Omicron in vitro Better than plasma antibodies.

Overall, the study results showed that vaccination enhanced sustained plasma and nasal IgG immune responses against the SARS-CoV-2 B.1 strain, Delta VOC, and Omicron VOC. However, her nasal IgA titers did not correlate with plasma IgA titers, decreased within 9 months, and were not significantly increased by COVID-19 vaccination. Our findings demonstrate that vaccination following natural SARS-CoV-2 infection fails to adequately recapitulate mucosal immune responses, leading to the development of a vaccine that induces durable and robust mucosal anti-SARS-CoV-2 immunity. emphasizes the need to

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .