Mucosal IgA response elicited by intranasal immunization of Lactobacillus plantarum expressing surface-displayed RBD protein of SARS-CoV-2

Abstract

Coronavirus Disease 2019 (COVID-19) caused by a novel betacoronavirus SARS-CoV-2 has been an ongoing global pandemic. Several vaccines have been developed to control the COVID-19, but the potential effectiveness of the mucosal vaccine remains to be documented. In this study, we constructed a recombinant L. plantarum LP18:RBD expressing the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein via the surface anchoring route. The amount of the RBD protein was maximally expressed under the culture condition with 200 ng/mL of inducer at 33 °C for 6 h. Further, we evaluated the immune response in mice via the intranasal administration of LP18:RBD. The results showed that the LP18:RBD significantly elicited RBD-specific mucosal IgA antibodies in respiratory tract and intestinal tract. The percentages of CD3 + CD4+ T cells in spleens of mice administrated with the LP18:RBD were also significantly increased. This indicated that LP18:RBD could induce a humoral immune response at the mucosa, and it could be used as a mucosal vaccine candidate against the SARS-CoV-2 infection. We provided the first experimental evidence that the recombinant L. plantarum LP18:RBD could initiate immune response in vivo, which implies that the mucosal immunization using recombinant LAB system could be a promising vaccination strategy to prevent the COVID-19 pandemic.

Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection

“…In particular, secretory IgA (S-IgA), located on the mucous membranes, plays a crucial role in mucosal immunity. In fact, this antibody can neutralize pathogens, particularly in respiratory tract infections caused by viruses, protecting the local mucosa from viral invasion [6]. SARS-CoV-2 infection results in a wide range of clinical signs, varying from asymptomatic to life-threatening acute respiratory distress syndrome, which is caused by a deleterious antiviral immune response in lungs [7].…”

“…Previous studies have shown that antibodies in the respiratory tract or oral cavity could be important for protecting against other human respiratory viruses like SARS-CoV, influenza virus, and respiratory syncytial virus (RSV) [6,9]. Nevertheless, in the fight against COVID-19, most attention has been given to circulating virus-neutralizing antibodies, especially IgG and IgM [10][11][12][13][14].…”

“…Recently, it has been demonstrated that the intranasal administration by adenovirusvectored vaccine encoding spike protein induced robust IgA and neutralizing antibody responses and prevented SARS-CoV-2 infection to both the upper and lower respiratory tract [6,34]. To this end, nasal and salivary antibodies could be relevant to demonstrate mRNA vaccines effects on the prevention of oral and nasal SARS-CoV-2 acquisition and transmission [16].…”

Intranasal COVID-19 vaccines: From bench to bed

“…Another Lactobacillus plantarum-based vaccine that expresses surface-displayed RBD of SARS-CoV-2 induced strong mucosal IgA (in respiratory and intestinal tracts) after IN immunization. 79 Further investigation is desired to evaluate bacterium-based vaccines’ immunogenicity and safety in bigger animal models to promote their clinical translation.…”

Hacking Commensal Bacteria to Consolidate the Adaptive Mucosal Immune Response in the Gut–Lung Axis: Future Possibilities for SARS-CoV-2 Protection

“…PgsA-Spike (S) protein segments SA (residues 2 to 114) and SB (residues 264 to 596) of SARS-CoV [88] Lactobacillus plantarum Mycobacterium tuberculosis, Fusion antigen AgE6 [89] Lactobacillus plantarum SARS-CoV-2 Spike protein (whole protein) [90] Lactobacillus plantarum Receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein [91] Novel vector host Francisella tularensis subsp. holarctica (single live multideletional attenuated) SARS-CoV-2 Spike, envelope, membrane, and nucleocapsid proteins [92] Mycobacterium paragordonae Receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein [93] In recent years, various gastrointestinal disease-causing bacteria have been tested as live-attenuated mucosal-delivery vaccine systems.…”