Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants

Abstract

The highly contagious SARS-CoV-2 Omicron subvariants severely attenuated the effectiveness of currently licensed SARS-CoV-2 vaccines based on ancestral strains administered via intramuscular injection. In this study, we generated a recombinant, replication-incompetent human adenovirus type 5, Ad5-S-Omicron, that expresses Omicron BA.1 spike. Intranasal, but not intramuscular vaccination, elicited spike-specific respiratory mucosal IgA and residential T cell immune responses, in addition to systemic neutralizing antibodies and T cell immune responses against most Omicron subvariants. We tested intranasal Ad5-S-Omicron as a heterologous booster in mice that previously received intramuscular injection of inactivated ancestral vaccine. In addition to inducing serum broadly neutralizing antibodies, there was a significant induction of respiratory mucosal IgA and neutralizing activities against Omicron subvariants BA.1, BA.2, BA.5, BA.2.75, BF.7 as well as pre-Omicron strains Wildtype, Beta, and Delta. Serum and mucosal neutralizing activities against recently emerged XBB, BQ.1, and BQ.1.1 could also be detected but were much lower. Nasal lavage fluids from intranasal vaccination contained multimeric IgA that can bind to at least 10 spike proteins, including Omicron subvariants and pre-Omicron strains, and possessed broadly neutralizing activities. Intranasal vaccination using Ad5-S-Omicron or instillation of intranasal vaccinee’s nasal lavage fluids in mouse nostrils protected mice against Omicron challenge. Taken together, intranasal Ad5-S-Omicron booster on the basis of ancestral vaccines can establish effective mucosal and systemic immunity against Omicron subvariants and multiple SARS-CoV-2 variants. This candidate vaccine warrants further development as a safe, effective, and user-friendly infection and transmission-blocking vaccine.

Development of a colloidal gold-based immunochromatographic assay for rapid detection of nasal mucosal secretory IgA against SARS-CoV-2

“…An increasing number of studies have found that high levels of nasal spike-sIgA antibodies, whether from previous infection with the wild-type SARS-CoV-2 or the Omicron variant, can reduce the risk of breakthrough Omicron infections (Havervall et al, 2022;Marking et al, 2023a,b). Currently, the detection of nasal spike-specific sIgA antibodies is mainly done through ELISA or electrochemiluminescence methods (Wang et al, 2023). However, these methods are complex, time-consuming, expensive, and difficult to apply for individuals.…”

“…Mucosal immune responses in the respiratory tract are vital for early restriction of viral replication and the clearance (Froberg and Diavatopoulos, 2021). SARS-CoV-2 infection can induce mucosal spike-specific sIgA that prevent viral invasion and reinfection (Sterlin et al, 2021;Tang et al, 2022;Wright et al, 2022;Wang et al, 2023). Several studies have reported that spikespecific mucosal IgA in bronchoalveolar lavages, saliva, or nasal swab samples can be detected in people who recovered from a SARS-CoV-2 infection (Sterlin et al, 2021;Havervall et al, 2022;Tang et al, 2022).…”

Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations

“…As a proof of concept, this shows the immense potential in converging these two streams for polyfunctional immunization schemes. Similarly, while IM + IN schemes have been the key focus in heterologous schemes [ 121 , 122 ], future research should explore combining other routes of administration (e.g., intradermal, subcutaneous, and enteric). Considering how some of these other routes may provide more robust and/or durable protection in certain antigen/adjuvant combinations, other combinations may prove more effective.…”

Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19

“…It is possible that secretory IgA could provide broader cross-reactivity against variants [98]. In a study by Wang et al [99], the administration of an intranasal Ad5-S-Omicron booster, in combination with ancestral vaccines, has been shown to establish robust mucosal and systemic immunity against Omicron variants. Furthermore, Zou et al [100] constructed a polymeric P5-22 IgG with 12 Fabs, which exhibits resistance to viral mutational escape.…”