[The Challenges of Vaccine Development Against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector]
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Published on: May 2, 2011
T A Zaichuk1, Y D Nechipurenko2,3, A A Adzhubey2,4
1Sendai Viralytics, Acton, MA, 117261 USA.
Abstract:
To design an effective and safe vaccine against betacoronaviruses, it is necessary to elicit a combination of strong humoral and cell-mediated immune responses as well as to minimize the risk of antibody-dependent enhancement of viral infection. This phenomenon was observed in animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV that were developed based on inactivated coronavirus or vector constructs expressing the spike protein (S) of the virion. The substitution and glycosylation of certain amino acids in the antigenic determinants of the S-protein, as well as its conformational changes, can lead to the same effect in a new experimental vaccine against SARS-CoV-2. This review outlines approaches for developing vaccines against the new SARS-CoV-2 coronavirus that are based on non-pathogenic viral vectors. For efficient prevention of infections caused by respiratory pathogens the ability of the vaccine to stimulate mucosal immunity in the respiratory tract is important. Such a vaccine can be developed using non-pathogenic Sendai virus vector, since it can be administered intranasally and induce a mucosal immune response that strengthens the antiviral barrier in the respiratory tract and provides reliable protection against infection. The mucosal immunity and the production of IgA antibodies accompanying its development reduces the likelihood of developing an antibody-dependent infection enhancement, which is usually associated only with immunopathological IgG antibodies.
Insights
Developing safe and effective betacoronavirus vaccines requires balancing humoral and cell-mediated immunity. Non-pathogenic viral vectors, like Sendai virus, can induce mucosal immunity, reducing antibody-dependent enhancement risks for SARS-CoV-2 prevention.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Designing effective vaccines against betacoronaviruses (e.g., SARS-CoV-1, MERS-CoV, SARS-CoV-2) necessitates eliciting robust humoral and cell-mediated immunity while mitigating antibody-dependent enhancement (ADE).
- Previous vaccine trials against SARS-CoV-1 and MERS-CoV, using inactivated viruses or spike protein (S) vector constructs, showed ADE risks.
- Alterations in S-protein antigenic determinants, including substitutions, glycosylation, and conformational changes, may exacerbate ADE in novel SARS-CoV-2 vaccines.
Purpose of the Study:
- To review strategies for developing SARS-CoV-2 vaccines utilizing non-pathogenic viral vectors.
- To highlight the importance of stimulating mucosal immunity in the respiratory tract for effective prevention of respiratory pathogen infections.
- To propose non-pathogenic Sendai virus as a suitable vector for intranasal vaccine delivery.
Main Methods:
- Review of existing literature on betacoronavirus vaccine development, focusing on viral vector approaches.
- Analysis of the mechanisms underlying mucosal immunity induction via intranasal administration.
- Evaluation of the role of different antibody isotypes (IgA vs. IgG) in vaccine-induced protection and ADE.
Main Results:
- Non-pathogenic viral vectors offer a promising platform for SARS-CoV-2 vaccine development.
- Intranasal administration of vaccines can induce mucosal immunity, strengthening the respiratory tract's antiviral barrier.
- Sendai virus vectors are capable of intranasal delivery and eliciting protective mucosal immune responses.
Conclusions:
- Vaccines based on non-pathogenic viral vectors, particularly Sendai virus administered intranasally, represent a viable strategy for SARS-CoV-2 prevention.
- Induction of mucosal immunity and IgA production is crucial for effective respiratory protection and may reduce ADE risk.
- This approach offers a potentially safer alternative to vaccines relying solely on systemic immunity or those prone to ADE.
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