Research roadmap for coronavirus vaccine development

Antibody response

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Antibody response

Research Question

Understanding of other species: Lack of comprehensive understanding of pets, livestock and wildlife immunology limits coronavirus vaccine research and development
Differences in antibody responses: Differences in antibody responses to coronavirus infection versus vaccination are not adequately understood
Immune mechanism: Understanding of immune mechanism of nonneutralising antibodies (ADCC, complement) and their potential for immune protection versus disease enhancement – can these be induced with different routes of vaccine administration?
Mechanism of humoral immunity: Differences in mechanism of humoral immunity between protection against infection (sterilising immunity) and protection from severe disease
Spike immunodominance: The spike is immunodominant over more conserved viral antigens, which may create obstacles for developing vaccines targeting more conserved domains of the virus
Immune imprinting: The role of immune imprinting and prior exposure to CoV infection or immunization. Measuring antibody response: Lack of qualified and harmonized methods to measure antibody responses other than ELISA. Lack of reagents. Pan-antibody identification: Identification of a pan-antibody with a broad spectrum of actions against different sarbecoviruses is challenging

Understanding generation of antibody responses: Conduct basic research to understand generation of antibody responses in pets, livestock and wildlife. Comparison of antibody responses for different species
Identify B cell response: Identify how distinct types of B cell responses (neutralizing antibodies against the spike and ADCC antibodies against
Mucosal immunity: Improve understanding of mucosal immunity. non-neutralizing conserved epitopes) synergize or compete to result in a protective response. Route of vaccine administration: Assess how the route of vaccine administration affects the protective immune response in the different immunologic compartments
Boosting strategies: Boosting strategies based on antigenic distance to avoid ‘back-boost’ due to immune imprinting
Pan-monoclonal antibodies: Identification and characterization of pan monoclonal antibodies (mAbs)

Develop functional assays to determine the range and breadth of protective antibody responses other than virus neutralization

Virus-neutralising antibodies directed against the coronavirus spike protein are critical in providing protective immunity following vaccination. Highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus have been isolated and characterised from a SARS-CoV survivor vaccinated (Chia et al., 2023, Sci. Adv. 9, eade3470)
Some studies suggests a unique strategy for selecting booster vaccines based on antigenic distance, which may be useful in designing future booster vaccines as new SARSCoV-2 variants emerge (Hu YF et al., Rational design of a booster vaccine against COVID-19 based on antigenic distance. Cell Host Microbe. 2023 Aug 9;31(8):1301-1316.e8. doi: 10.1016/j.chom.2023.07.004 )