Vaccine efficacy against COVID-19: A foresight on the host-associated factors

Abstract

To the Editor, On the wake of the ongoing coronavirus disease 2019 (COVID-19) pandemic, global dependence current lies on the development of an efficient vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prior to licensure, the safety, immunogenicity and protective effects of a vaccine are evaluated in trials based on assessment criteria such as efficacy. Vaccine efficacy measures reduction in the risk of infection in vaccinated individuals relative to that of unvaccinated individuals under optimal conditions (Phase III randomized controlled trials); whereas the same parameter measured in the real world i.e. field conditions (Phase IV non-randomized observational studies) can be called as vaccine effectiveness. The endpoints to be monitored in vaccine efficacy trials may be primary, such as the occurrence of symptomatic disease with confirmed etiology; or secondary, such as SARS-CoV-2 infection or viral shedding. 1 Notwithstanding the efforts to develop a vaccine with the concept of ‘one size fits all’, various factors might contribute to individual differences in vaccine efficacy. Apart from the factors related to viral properties, environment, technical and social interventions; the host-associated factors impacting the vaccine efficacy need to be unravelled for the development of a universal vaccine with reliably long-lasting immunity. Host-specific factors which may serve as correlates of protection, although not yet outlined for vaccine-induced immunity against COVID-19, may include age, comorbidities, behaviour, biological sex, immune history, genetics, commensal microbiota and pregnancy (Fig. 1 ); as also outlined for the vaccines against other viruses such as influenza. 2 Figure 1 Hypothetical impact of host-associated factors on the vaccine efficacy against COVID-19. Figure 1 Immunosenescence of the innate and adaptive immune system occurs as a result of age-related changes, which might lead to reduced vaccine efficacy in aged individuals falling under the high-risk group for COVID-19. People with underlying health conditions (comorbidities e.g. chronic respiratory disease, cardiovascular disease, immunocompromised, obesity, diabetes, renal or liver disease, cancer) also belong to the high-risk group. Thus the disproportionate SARS-CoV-2 affection and mortality of older individuals and those with comorbidities necessitates the need for their active enrolment and tracking in efficacy trials apart from young adults. Also, there is a need for a greater understanding of paediatric immunology against COVID-19 before the initiation of vaccine efficacy studies since children are not much affected by COVID-19. Behavioural factors might affect vaccine efficacy especially in studies relying on the natural infection, for e.g. older individuals could be less likely to get exposed to SARS-CoV-2 because of avoidance of social gatherings or public transport. Conversely, healthcare workers may have higher exposure to SARS-COV-2 as per their occupational behaviour as compared to other participants in vaccine efficacy trials. 3 Although the impact of biological sex on immune response against SARS-CoV-2 is still unexplored but severe disease and higher mortality have been reported in the male sex. 4 This might be due to sex-associated variation in the immune response but confirmatory efficacy trial based studies, including the mediation of sex steroids (mainly oestrogen, progesterone and testosterone), are required to compare the levels of protection (in terms of parameters such as neutralizing antibody response, Tlr expression in B cells, CD4+ and CD8+ T cell response, etc.) achieved by vaccine-induced immunity in either sex. Immune imprinting may occur through prior exposure to SARS-CoV-2 via infection or vaccination. The documented re-infection of SARS-CoV-2 suggests receding severity indicating the priming of adaptive immunity. 5 The induction of immune imprinting by various vaccine platforms needs to be well characterized based on the relative efficacy trials. The genetic dissimilarity can cause individual differences in protective immunity and hence the vaccine efficacy. The reason of genetic advantage could be the variations in binding specificities of human leucocyte antigen (HLA) molecules of a haplotype with SARS-CoV-2 peptides on antigen-presenting cells (APC). Dedicated studies are required to understand these biomarkers of immunological protection and deduce their effects on vaccine efficacy. This inturn could also explain the demographic variations like higher severity and mortality in Asian, Black and minority ethnicities. 3 The commensal microbiota plays a crucial role in innate and adaptive immunity. Immunological benefits of adding probiotics in vaccine formulations or consumption prior to immunization have been proved for viruses like influenza. 2 Studies should be conducted to evaluate the impact of respiratory and intestinal microbiota (and association with factors like sex and age) on the SARS-CoV-2 infection, immunity and vaccine efficacy. The physiological and immunological changes such as variations in immunomodulatory hormones, cytokines and immune cells associated with innate and adaptive immunity occur in different stages of pregnancy. Thus, the impact of vaccine-induced immunity on pregnant females needs to be actively monitored to develop an efficacious vaccine without any adverse effect on maternal and foetal health. Conclusively, as the global efforts are underway to develop a highly efficacious vaccine against SARS-CoV-2, various host-associated factors must be duly considered and explored to mitigate the inconsistencies in vaccine efficacy across different risk groups so that a universal COVID-19 vaccine can be developed. CRediT authorship contribution statement Priyanka: Conceptualization, Data Curation, Visualization, Writing - Original Draft, Writing - review & editing. Om Prakash Choudhary: Conceptualization, Supervision, Writing - Original Draft, Writing - review & editing. Ethical approval This article does not require any human/animal subjects to acquire such approval. Funding There is no funding source used for this paper. Declaration of Competing Interest The authors have no conflicts of interest relevant to this article.