A review of leading COVID-19 vaccines, the quest for immune protection, and its key challenges. Part 3: Covid-19 vaccines – Key challenges and translational science
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Date
2021-05-06
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Abstract
Rationale
• Developing and deploying safe and effective COVID-19 vaccines are faced with many challenges and unanswered questions.
• Massive amounts of heterogenic scientific data are being generated that are needed rapidly to advance vaccine development, protect people and restore normality.
• The purpose of Part 3 of this four-part series is to review the scientific considerations related to key challenges associated with COVID-19 vaccines and immune protection with the focus of making this data more meaningful and open for clinicians.
Key points
• The primary immunogen (antigen) required to induce neutralising antibodies (humoral) and T cell (cellular) immune responses is the S-protein fragment of SARS-CoV-2.
• Currently, the evidence is firmly pointing towards neutralising antibodies, being more critical for protection.
• Long-term protective or durable immune memory is driven by virus-specific T cell and B cell responses (adaptive immunity).
• Circulating antibody titres are not predictive of T cell immune memory.
• Durable immune memory is a crucial factor to sustain herd immunity.
• Adjuvants are added to certain vaccines to provoke a more robust and durable immune response.
• Adjuvants that provoke TH1-biased immune responses are preferred.
• 90% of adults are seropositive for 'common cold' CoV strains.
• There is a cross-reactivity between specific T cell of SARS-CoV-2 and 'common cold' CoV's.
• Prior infection with 'common cold' can play a potentially protective role.
• Seropositive individuals present with a rapid and higher antibody immune response after a single dose with an mRNA vaccine.
• Vaccine-induced immune responses resulting in non-neutralising antibodies, low antibody titres, and abnormal T cell responses (TH2- biased) are potential risks for serious enhanced disease events but unlikely events.
• Vaccine strategies aimed at inducing high titres on neutralising antibodies and TH1- biased immune responses reduce the risk of serious adverse events.
• Emerging variants of concern are extremely infectious, highly transmissible and threatens the protective efficacy of current vaccines.
Public health implications
• A rapid global vaccination campaign combined with standard mitigation measures to stop transmission is the best defence against the emergence of further SARS-CoV-2 variants and the safest way to attain herd immunity.
• Booster immunisations may be required to promote or improve the durability and strength of vaccine immunity.
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Keywords
adjuvants, coronavirus, COVID-19 vaccines, herd immunity, immune escape, immune memory, immunogen, neutralising antibodies, SARS-CoV-2 variants, vaccination, vaccine-induced disease