Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses

Abstract

ver the past two decades, the world has experienced a substantial number of disease outbreaks from viral infections including yellow fever, dengue fever, Ebola, Zika, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome and the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic 1 . The SARS-CoV-2 pandemic has illuminated how disruptive sustained infectious disease outbreaks can be on society. Given the unpredictability of when the next pandemic will emerge, strengthening our ability to respond rapidly to any infectious disease threat is a global priority.In what may be one of the most impressive accomplishments of modern medicine, multiple effective vaccines were developed against SARS-CoV-2 in less than 12 months after the initial outbreak. As of February 2022 ten coronavirus disease 2019 (COVID-19) vaccines are currently approved for full or emergency use authorization by the World Health Organization (https://covid19.trackvaccines.org/agency/who/). These approved vaccines span four distinct vaccine platforms, providing an additional layer of diversity in potential vaccine responses. The Moderna and Pfizer-BioNTech vaccines both use modified mRNAs to produce antigen upon vaccination 2,3 . Both vaccines use lipid nanoparticle-encapsulated formulations to deliver mRNA that encodes for a prefusion stabilized, full-length SARS-CoV-2 spike (S) protein. The Johnson & Johnson (Ad26 vector) and AstraZeneca AZD1222 (ChAdOx1 vector) vaccines use distinct replication-incompetent adenoviral vectors to deliver antigen (the prefusion stabilized, full-length S protein) 4,5 . The Sinopharm and Sinovac-CoronaVac platforms utilize β-propiolactone-inactivated virus produced in Vero E6 cells and are formulated with the adjuvant alum to promote immunogenicity 6,7 . Protein subunit-based platforms are in advanced stages of development, with one approved for emergency use authorization in Indonesia (Novavax 8 ; clinical trial no. NCT04742738). Approved vaccines have efficacy rates of ~50-95%, with Moderna and Pfizer exhibiting the highest rates of short-term efficacy.

Cellular Immune Response to BNT162b2 mRNA COVID-19 Vaccine in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital

“…Among the different methods to evaluate T-cell responses to SARS-CoV-2 vaccination there are interferon-gamma releasing assays (IGRA), that provide a quantitative measure of cellular immune response as levels of specifically secreted IFN-γ and are used in other clinical contexts, such as transplantation [ 5 ]. Currently, the literature on the dynamics and magnitude of cellular response in vaccinated individuals is still limited [ 6 , 7 , 8 ], particularly regarding the duration of T-cell responses after vaccination [ 9 , 10 , 11 , 12 , 13 ] and the factors that could explain the interindividual heterogeneity in immunological response [ 14 ].…”

COVID-19 Vaccination Is Safe among Mast Cell Disorder Patients, under Adequate Premedication

“…Both membrane-bound and cytosolic pattern recognition receptors can recognize different components of the vaccines. In the case of mRNA vaccines, the lipid nanoparticle may be recognized by Toll-like receptor (TLR) 4, and mRNA by both TLR7 and melanoma differentiation-associated protein 5 (MDA5), while TLR9 may recognize DNA in adenovirus vector vaccines (reviewed in [ 31 ]).…”

Immune response in COVID-19: what is next?

“…A successful vaccine relies on various factors such as the identification of the effective epitopes or viral components, the delivery vectors, proper adjuvant, administration routes and the physical and medical conditions of the recipients [ 156 ]. Even if we have effective vaccines, the vaccination rate in a given time, social acceptability/resistance, and inadequate social distance may allow the virus to present in a population for sufficiently long to mutate [ 157 ].…”