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

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.