Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology

Hemmi, Takuya; Ainai, Akira; Hanabusa, Takao; Tobiume, Minoru; Kuriyama, Takayuki; Iwata‐Yoshikawa, Naoko; Iida, Shun; Sato, Yuko; Miyamoto, Shô; Ueno, Akira; Sano, Kaori; Saito, Shinji; Shiwa-Sudo, Nozomi; Nagata, Noriyo; Tamura, Koji; Suzuki, Ritsuro; Hasegawa, Hideki; Suzuki, Tadaki

doi:10.1016/j.vaccine.2022.08.049

Cited by 11 publications

(10 citation statements)

References 46 publications

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“…IgA is known to be a potent neutralizer [35][36][37] and a strong driver of opsinophagocytic function 38 . Due to its polyfunctionality and mucosal localization, vaccine formulations and platforms have sought to enhance IgA responses 34,[39][40][41][42] . Our study supports the notion that vaccine delivery route can greatly impact mucosal IgA induction.…”

Section: Discussionmentioning

confidence: 99%

Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques

Tong,

Wang,

Jung

et al. 2024

Preprint

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Antibodies represent a primary mediator of protection against respiratory viruses such as SARS-CoV-2. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are not well understood. Here we show that antibody correlates of protection against SARS-CoV-2 challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, neutralizing antibodies were the strongest correlate of protection and were linked to Spike-specific binding antibodies and other extra-neutralizing antibody functions that create a larger protective network. In contrast, in bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal Spike-specific IgG, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites. The correlation of ADCP and other Fc functional antibody responses with protection in BAL suggests that these antibody responses may be critical for protection against SARS-CoV-2 Omicron challenge in mucosa.

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Section: Discussionmentioning

confidence: 99%

Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques

Tong,

Wang,

Jung

et al. 2024

Preprint

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“…In mice, Th1 cells produce IFN-γ resulting in IgG2a induction. In contrast, Th2 cells produce IL-4 and IL-5, inducing IgG1 responses [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of FMD virus-like particles in yeast Hansenula polymorpha and immunogenicity of combine with CpG and aluminum adjuvant

Zhang

Ge²,

Ju-yin

et al. 2023

J Vet Sci

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Background Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. Objectives The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. Methods BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. Results The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4 + T cells were observed in mice immunized with VLPs. Conclusions The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

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“…Data from preclinical trials suggest that the mucosal vaccines elicit not only systemic immune responses but mucosal immune responses as well, which is equally or more potent than the systemic immunization-elicited immunity in controlling SARS-CoV-2 infection. A very important feature of IN-delivered mucosal vaccines is that they also induce cross-protection against variants including the Alpha, Beta, Gamma, and Omicron variants [154][155][156][157]. IN immunization-induced mucosal immunity is associated with secretory IgA [154,158] and CD4 and CD8 T cell-mediated immune response.…”

Section: Mucosal Vaccinesmentioning

confidence: 99%

“…A very important feature of IN-delivered mucosal vaccines is that they also induce cross-protection against variants including the Alpha, Beta, Gamma, and Omicron variants [154][155][156][157]. IN immunization-induced mucosal immunity is associated with secretory IgA [154,158] and CD4 and CD8 T cell-mediated immune response. With regard to immunity against SARS-CoV-2, viral neutralization by the secretory Abs is considered to be the key mechanism.…”

Section: Mucosal Vaccinesmentioning

confidence: 99%

“…With regard to immunity against SARS-CoV-2, viral neutralization by the secretory Abs is considered to be the key mechanism. Evidence suggests that T cell-mediated immunity also contributes significantly [154,156,157], and in some cases, T cell-mediated immunity alone in absence of a spike-specific Ab response is sufficient in controlling the SARS-CoV-2 challenge [92]. In addition, preliminary evidence indicates that IN immunization is also effective in transmission blocking [159,160], which may have a far greater impact on the rapid containment of pandemics.…”

Section: Mucosal Vaccinesmentioning

confidence: 99%

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SARS-CoV-2: Immunity, Challenges with Current Vaccines, and a Novel Perspective on Mucosal Vaccines

2023

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The global rollout of COVID-19 vaccines has played a critical role in reducing pandemic spread, disease severity, hospitalizations, and deaths. However, the first-generation vaccines failed to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission, partially due to the limited induction of mucosal immunity, leading to the continuous emergence of variants of concern (VOC) and breakthrough infections. To meet the challenges from VOC, limited durability, and lack of mucosal immune response of first-generation vaccines, novel approaches are being investigated. Herein, we have discussed the current knowledge pertaining to natural and vaccine-induced immunity, and the role of the mucosal immune response in controlling SARS-CoV2 infection. We have also presented the current status of the novel approaches aimed at eliciting both mucosal and systemic immunity. Finally, we have presented a novel adjuvant-free approach to elicit effective mucosal immunity against SARS-CoV-2, which lacks the safety concerns associated with live-attenuated vaccine platforms.

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Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology

Cited by 11 publications

References 46 publications

Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques

Compartment-Specific Antibody Correlates of Protection to SARS-CoV-2 Omicron in Macaques

Expression of FMD virus-like particles in yeast Hansenula polymorpha and immunogenicity of combine with CpG and aluminum adjuvant

SARS-CoV-2: Immunity, Challenges with Current Vaccines, and a Novel Perspective on Mucosal Vaccines

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