Nasal vaccine candidate: Two-in-one protection against Covid-19

Nasal vaccine candidate

Nasal protein and vector vaccines have so far failed to achieve sufficient efficacy against COVID-19. Chinese researchers have now combined the two approaches in a vaccine candidate – with greater success.

Research teams around the world have been working on a nasally administered coronavirus vaccine since the identification of the SARS-CoV-2 pandemic pathogen – so far with little success. / © Adobe Stock/LP

Only mucosal immunity will effectively protect against upper respiratory tract infections caused by SARS-CoV2. This is the scientific consensus. Yet, no nasally administered COVID-19 vaccines are currently approved globally. Both traditional subunit vaccines, which contain individual proteins, and vector vaccines, which deliver instructions for vaccine antigens into cells, have so far failed to provide sufficient protection in studies. Now, Chinese researchers are reporting the development of a nasal vaccine candidate that combines the two approaches, which are intended to reinforce each other.

Researchers led by Weiqi Hong from the West China Hospital of Sichuan University in Chengdu, China, present a vaccine candidate in a publication in the scientific journal "Nature Biomedical Engineering." It contains an adenovirus vector encoding the spike protein of the XBB.1.5 variant (Ad5XBB.1.5). The vaccine also contains two trimeric recombinant proteins, i.e., proteins composed of three identical, artificially produced components. One originates from the receptor-binding domain of the XBB variant (RBDXBB.1.5-HR), and the second from the receptor-binding domain of BA.5 (RBDBA.5-HR). The idea behind it: The vector—as a virus—stimulates the vaccinated person's immune system through various mechanisms and thus also serves as an adjuvant (enhances the efficacy) for the protein component.

This appears to work: The researchers demonstrated in animal experiments that the two-component vaccine (Ad5XBB.1.5 plus RBDXBB.1.5-HR) induces superior humoral and cellular immunity against XBB.1.5 variants compared to the individual components. In mice, the vaccine also protected against infection with the XBB.1.16 virus, and it prevented transmission of the XBB.1.5 virus in a hamster model. By adding the third antigen component (Ad5XBB.1.5 + RBDXBB.1.5-HR + RBDBA.5-HR), the spectrum of protection is even broader and broader in its neutralization.

The team reports that the activation of the so-called STING signaling pathway in mucosal cells is essential for the adjuvant effect of the adenovirus vector. The protein "STING" (stimulator of interferon genes ) recognizes double-stranded DNA (dsDNA) in the cytoplasm, where it is only found when pathogens have invaded or the cell is malfunctioning. Both alert the innate immune system.