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Front Immunol ; 12: 748103, 2021.
Article in English | MEDLINE | ID: covidwho-1555317


COVID-19-specific vaccines are efficient prophylactic weapons against SARS-CoV-2 virus. However, boosting innate responses may represent an innovative way to immediately fight future emerging viral infections or boost vaccines. MV130 is a mucosal immunotherapy, based on a mixture of whole heat-inactivated bacteria, that has shown clinical efficacy against recurrent viral respiratory infections. Herein, we show that the prophylactic intranasal administration of this immunotherapy confers heterologous protection against SARS-CoV-2 infection in susceptible K18-hACE2 mice. Furthermore, in C57BL/6 mice, prophylactic administration of MV130 improves the immunogenicity of two different COVID-19 vaccine formulations targeting the SARS-CoV-2 spike (S) protein, inoculated either intramuscularly or intranasally. Independently of the vaccine candidate and vaccination route used, intranasal prophylaxis with MV130 boosted S-specific responses, including CD8+-T cell activation and the production of S-specific mucosal IgA antibodies. Therefore, the bacterial mucosal immunotherapy MV130 protects against SARS-CoV-2 infection and improves COVID-19 vaccines immunogenicity.

Bacteria/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Administration, Mucosal , Animals , Antibodies, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Immunity, Heterologous , Immunity, Innate , Immunogenicity, Vaccine , Immunoglobulin A/immunology , Immunologic Factors/administration & dosage , Immunologic Factors/immunology , Mice , Vaccination
Adv Drug Deliv Rev ; 160: 234-243, 2020.
Article in English | MEDLINE | ID: covidwho-1023400


The Coronavirus disease 2019 (COVID-19) pandemic has led to a surge in need for alternative routes of administration of drugs for end of life and palliative care, particularly in community settings. Transmucosal routes include intranasal, buccal, sublingual and rectal. They are non-invasive routes for systemic drug delivery with the possibility of self-administration, or administration by family caregivers. In addition, their ability to offer rapid onset of action with reduced first-pass metabolism make them suitable for use in palliative and end-of-life care to provide fast relief of symptoms. This is particularly important in COVID-19, as patients can deteriorate rapidly. Despite the advantages, these routes of administration face challenges including a relatively small surface area for effective drug absorption, small volume of fluid for drug dissolution and the presence of a mucus barrier, thereby limiting the number of drugs that are suitable to be delivered through the transmucosal route. In this review, the merits, challenges and limitations of each of these transmucosal routes are discussed. The goals are to provide insights into using transmucosal drug delivery to bring about the best possible symptom management for patients at the end of life, and to inspire scientists to develop new delivery systems to provide effective symptom management for this group of patients.

COVID-19 Drug Treatment , COVID-19/epidemiology , Drug Delivery Systems/methods , Palliative Care/methods , Terminal Care/methods , Administration, Mucosal , COVID-19/metabolism , Humans , Pandemics
Front Immunol ; 11: 1959, 2020.
Article in English | MEDLINE | ID: covidwho-732901


The lung is the vital target organ of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the majority of patients the most active virus replication seems to be found in the upper respiratory tract, severe cases however suffer from SARS-like disease associated with virus replication in lung tissues. Due to the current lack of suitable anti-viral drugs the induction of protective immunity such as neutralizing antibodies in the lung is the key aim of the only alternative approach-the development and application of SARS-CoV-2 vaccines. However, past experience from experimental animals, livestock, and humans showed that induction of immunity in the lung is limited following application of vaccines at peripheral sides such as skin or muscles. Based on several considerations we therefore propose here to consider the application of a Modified Vaccinia virus Ankara (MVA)-based vaccine to mucosal surfaces of the respiratory tract as a favorable approach to combat COVID-19.

Betacoronavirus/chemistry , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Vaccinia virus/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Administration, Mucosal , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Bronchi/immunology , COVID-19 , Coronavirus Infections/virology , Humans , Immunoglobulin A/metabolism , Lymphoid Tissue/immunology , Plasma Cells/immunology , Pneumonia, Viral/virology , Respiratory Mucosa/drug effects , Respiratory Mucosa/immunology , SARS-CoV-2 , T-Lymphocytes/immunology , Vaccination , Vaccines, Attenuated/immunology