Strategies for intranasal delivery of SARS-CoV-2 and other respiratory disease vaccines.
1 Purpose
We aim to adapt our albumin-based intranasal subunit vaccine strategy in the context of the SARS-CoV-2 vaccine. Several studies support that the neonatal Fc receptor (FcRn), which is broadly expressed by epithelial cells in the lungs and endothelial cells in the blood vessels, mediates bidirectional mucosal transport and recycling of both IgG and albumin. Thus, with their natural long half-life of about 3 weeks, albumin may be utilized as a FcRn targeting moiety to enhance the vaccine efficacy against coronavirus. Moreover, albumin can be engineered for improved FcRn binding and transport properties. Generally, recombinant albumin molecules are stable and easy to produce, which should result in a cost-effective vaccine.
We fuse subunit targets of SARS-CoV-2 and other respiratory viruses to albumin with the aim to elicit an immune response that will neutralize viral infectivity. Considering cross-species differences between mice and humans, we will test the developed subunit vaccines in both conventional BALB/c mice and transgenic mice expressing human FcRn, with or without expression of human IgG1 Fc. Since it is not possible to mimic human immune responses in vitro, the use of mouse models is preferred as mice possess similarities to humans concerning the immune system. As we do not have the possibility to implement a SARS-CoV-2 challenge study, this will not be included. Nevertheless, we hope that the study outcomes will lead to a collaboration with new partnerships and actors, and eventually innovative vaccine development against COVID-19 as well as other respiratory diseases.
2 Distress
We have prior experience in strategies for intranasal delivery of albumin-based vaccines, and it is not expected that the mice will suffer from the delivery process or the administered compounds.
3 Expected benefit
There is a global need for the development of new vaccines and vaccine strategies. Most vaccines are administered subcutaneously or intramuscularly, and immune protection at the site of infection may be inadequate. Non-invasive delivery methods, such as intranasal delivery, may reduce the risk of infection and hazardous waste following the use of needles and syringes, and improve patient convenience and compliance. In the fight against viral infections affecting lung mucosa, the intranasal strategy is of importance, as it may result in higher local protection since both the vaccine unit and the viral target are at the same site.
4 Number of animals
- 802 BALB/c mice
- 50 C57BL/6
- 708 hFcRn Tg32 mice (B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ)
- 1908 Tg32-hFc mice (B6.Cg-Tg(FCGRT)32Dcr Fcgrttm1Dcr Ighg1em2(IGHG1)Mvw/MvwJ)
5 How to adhere to 3R
Highly qualified personnel will take care of the research animals, mice will have an enriched environment, and we will minimize stress by handing the animals gently and in a quiet surrounding. By a thorough characterization using biochemical and cellular methods, we have limited the number of albumin-vaccine candidates of interest to an absolute minimum. Nevertheless, in vivo models are necessary to evaluate the pharmacokinetics and immune responses of the developed vaccines, which depend on several factors that cannot be measured in vitro.
We aim to adapt our albumin-based intranasal subunit vaccine strategy in the context of the SARS-CoV-2 vaccine. Several studies support that the neonatal Fc receptor (FcRn), which is broadly expressed by epithelial cells in the lungs and endothelial cells in the blood vessels, mediates bidirectional mucosal transport and recycling of both IgG and albumin. Thus, with their natural long half-life of about 3 weeks, albumin may be utilized as a FcRn targeting moiety to enhance the vaccine efficacy against coronavirus. Moreover, albumin can be engineered for improved FcRn binding and transport properties. Generally, recombinant albumin molecules are stable and easy to produce, which should result in a cost-effective vaccine.
We fuse subunit targets of SARS-CoV-2 and other respiratory viruses to albumin with the aim to elicit an immune response that will neutralize viral infectivity. Considering cross-species differences between mice and humans, we will test the developed subunit vaccines in both conventional BALB/c mice and transgenic mice expressing human FcRn, with or without expression of human IgG1 Fc. Since it is not possible to mimic human immune responses in vitro, the use of mouse models is preferred as mice possess similarities to humans concerning the immune system. As we do not have the possibility to implement a SARS-CoV-2 challenge study, this will not be included. Nevertheless, we hope that the study outcomes will lead to a collaboration with new partnerships and actors, and eventually innovative vaccine development against COVID-19 as well as other respiratory diseases.
2 Distress
We have prior experience in strategies for intranasal delivery of albumin-based vaccines, and it is not expected that the mice will suffer from the delivery process or the administered compounds.
3 Expected benefit
There is a global need for the development of new vaccines and vaccine strategies. Most vaccines are administered subcutaneously or intramuscularly, and immune protection at the site of infection may be inadequate. Non-invasive delivery methods, such as intranasal delivery, may reduce the risk of infection and hazardous waste following the use of needles and syringes, and improve patient convenience and compliance. In the fight against viral infections affecting lung mucosa, the intranasal strategy is of importance, as it may result in higher local protection since both the vaccine unit and the viral target are at the same site.
4 Number of animals
- 802 BALB/c mice
- 50 C57BL/6
- 708 hFcRn Tg32 mice (B6.Cg-Fcgrttm1Dcr Tg(FCGRT)32Dcr/DcrJ)
- 1908 Tg32-hFc mice (B6.Cg-Tg(FCGRT)32Dcr Fcgrttm1Dcr Ighg1em2(IGHG1)Mvw/MvwJ)
5 How to adhere to 3R
Highly qualified personnel will take care of the research animals, mice will have an enriched environment, and we will minimize stress by handing the animals gently and in a quiet surrounding. By a thorough characterization using biochemical and cellular methods, we have limited the number of albumin-vaccine candidates of interest to an absolute minimum. Nevertheless, in vivo models are necessary to evaluate the pharmacokinetics and immune responses of the developed vaccines, which depend on several factors that cannot be measured in vitro.