Single-dose intranasal subunit vaccine rapidly clears secondary sepsis in a high-dose pneumonic plague infection

D’Arco, Christina; McCormick, Alison A.; Arnaboldi, Paul M.

doi:10.1016/j.vaccine.2021.01.040

“…Both vaccines, rF1 + rV and rV10, were tested and demonstrated efficacy against pneumonic plague infection in mice, guinea pigs and Cynomolgus macaques [176,177] but not in African green monkeys [125]. Further investigations of enhancing immunogenicity or delivery of these subunit vaccines have been attempted or are ongoing by several groups [178][179][180][181][182][183][184][185]. Y. pestis is a Gramnegative bacterium that expresses multiple potential targets that have been exploited for the development of novel medical countermeasures.…”

Section: Vaccinesmentioning

confidence: 99%

Plague Prevention and Therapy: Perspectives on Current and Future Strategies

Rosario-Acevedo

¹

,

Biryukov

²

,

Bozue

³

et al. 2021

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Plague, caused by the bacterial pathogen Yersinia pestis, is a vector-borne disease that has caused millions of human deaths over several centuries. Presently, human plague infections continue throughout the world. Transmission from one host to another relies mainly on infected flea bites, which can cause enlarged lymph nodes called buboes, followed by septicemic dissemination of the pathogen. Additionally, droplet inhalation after close contact with infected mammals can result in primary pneumonic plague. Here, we review research advances in the areas of vaccines and therapeutics for plague in context of Y. pestis virulence factors and disease pathogenesis. Plague continues to be both a public health threat and a biodefense concern and we highlight research that is important for infection mitigation and disease treatment.

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“…Since nasal epithelial cells are a primary target for SARS-CoV-2, intranasal vaccinations that induce S-IgA in the upper respiratory tract are desirable for protection against the infection and transmission of the virus ( Sungnak et al, 2020 ). To date, some intranasal vaccines are under development and have shown a robust mucosal and humoral immune responses in human and animal models ( Houston, 2023 ) ( Chavda et al, 2021 ) ( Alu et al, 2022 ) ( Barrett et al, 2021, Bricker et al, 2021, D’Arco et al, 2021, Kim et al, 2021 ) ( Vabret et al, 2020 ) ( Ohtsuka et al, 2021 ). Considerable efforts have been made to develop mucosal vaccines against pathogens, and nasal lavage fluids containing polyclonal S-IgAs have been used to evaluate the response to these vaccinations ( Maltseva et al, 2022 ) ( Gianchecchi et al, 2019 ) ( Wong et al, 2022 ) ( Afkhami et al, 2022 ) ( Sui et al, 2021 ) ( Azzi et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

Waki

¹

,

Tani

²

,

Saga

³

et al. 2023

Preprint

0

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Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgAs), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, the evaluation of intranasal vaccine efficacy is based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgAs induced by intranasal vaccines, we developed 99 monoclonal IgAs from nasal mucosa and 114 monoclonal IgAs or IgGs from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgAs exhibited shared origins and both common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking and SARS-CoV-2 virus neutralization of monomeric and multimeric IgA pairs recognizing different epitopes showed that even nonneutralizing monomeric IgA, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. Our investigation is the first to demonstrate the function of nasal IgAs at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of virus infection.

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“…Since nose epithelial cells are a primary target for SARS-CoV-2, internasal vaccinations that induce S-IgA in the upper respiratory tract are desirable for protection against the infection and transmission of the virus (Sungnak et al, 2020 ). To date, some internasal vaccines are under development and have shown a robust mucosal and humoral immune responses in human and animal models (Houston, 2023 ) (Chavda et al, 2021 ) (Alu et al, 2022 ) (Barrett et al, 2021, Bricker et al, 2021, D'Arco et al, 2021, Kim et al, 2021 (Vabret et al, 2020 ) (Ohtsuka et al, 2021 ). Considerable efforts have been made to develop mucosal vaccines against pathogens, and nasal lavage fluids containing polyclonal S-IgAs have been used to evaluate the response to these vaccinations (Maltseva et al, 2022 ) (Gianchecchi et al, 2019 ) (Wong et al, 2022 ) (Afkhami et al, 2022 ) (Sui et al, 2021 ) (Azzi et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

Waki,

Tani,

Saga

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgAs), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, the evaluation of intranasal vaccine efficacy is based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgAs induced by intranasal vaccines, we developed 99 monoclonal IgAs from nasal mucosa and 114 monoclonal IgAs or IgGs from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgAs exhibited shared origins and both common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking and SARS-CoV-2 virus neutralization of monomeric and multimeric IgA pairs recognizing different epitopes showed that even nonneutralizing monomeric IgA, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. Our investigation is the first to demonstrate the function of nasal IgAs at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of virus infection.

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Single-dose intranasal subunit vaccine rapidly clears secondary sepsis in a high-dose pneumonic plague infection

Cited by 4 publications

References 43 publications

Plague Prevention and Therapy: Perspectives on Current and Future Strategies

Plague Prevention and Therapy: Perspectives on Current and Future Strategies

Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

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