Vaccines against SARS-CoV-2 have been made in a record time. However, although the vaccines that have been deployed have clearly reduced the percentage of severe infections in countries where they have been widely used, many developing countries have problems to afford the purchase and/or distribution of approved vaccines. In addition, current vaccines provide with limited mucosal immunity to appropriately prevent infections. New efficacious and safe SARS-CoV-2 vaccines that could be manufactured locally in developing countries, that would not require ultra-congelation and that would induce infection-preventing mucosal immunity are desirable. We have been working in the development of such a vaccine based on a Newcastle disease virus (NDV) vector. This avian virus is widely used as live and inactivated vaccine in poultry against Newcastle disease, a potentially devastating avian disease. NDV inoculation in mammals results in abortive infection due to the induction of a robust local innate immune response that inhibits further virus replication while potentiating the induction of adaptive immune responses. NDV vaccines are manufactured using the same technology as most of the influenza virus vaccines, making it possible its production in most developing countries. We have generated NDV-based vaccines expressing a stabilized version of the S protein of SARS-CoV-2. These vaccines are stable at 2 degrees and provide protection against SARS-CoV-2 and its variants in animal models. NDV-based vaccines not only express the vaccine antigen in infected cells, but also incorporate the antigen into the virion, making it possible the use of either live or inactivated versions of the vaccine. Results from phase I clinical trials demonstrated lack of severe adverse events and very mild reactogenicity, as well as the induction of a robust T cell and neutralizing antibody response against SARS-CoV-2. Additional clinical trials have been initiated using live intranasal administration which has the potential to generate a more potent mucosal immunity for prevention of not only disease but also asymptomatic infections and transmission.

Learning Objectives:

1. Explain how mucosal immunity is required to prevent respiratory virus infections.

2. Discuss current COVID-19 vaccines and how they are highly effective in preventing severe disease, but less efficient in preventing reinfections.

3. Discuss how new generation of COVID-19 vaccines that prevent both severe disease and infection/transmission are desirable.