Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake

Abstract

Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity.

High-resolution kinetics and cellular determinants of antibody response to SARS-CoV-2 over two years after COVID-19 vaccination

“…All participants had detectable antibody responses 25 months after the 1 st vaccine dose and 15 months after the booster (3 rd ) dose, which is in line with our previous study 12 . Our findings confirm the kinetic pattern of IgG and IgA surges following subsequent immunizations, which restore and increase humoral responses, previously observed 9,[30][31][32] . It also aligns with a few studies that have reported a non-constant decelerating waning of antibodies after COVID-19 vaccination and SARS-CoV-2 infection 8,33,34 , which results in a biphasic decline with an initial rapid decay during the first few months, followed by a phase of slower decline and stabilization.…”

Clinical Assessment of SARS-CoV-2 Antibodies in Oral Fluids Following Infection and Vaccination

“…From a clinical standpoint, threshold values of spike- and nucleocapsid-specific IgG and/or SIgA in mucosal sites may serve as more specific and accessible indicators of immunity compared to immunoglobulins found in serum/plasma, potentially influencing decisions about the need for booster vaccinations in high-risk and vulnerable populations ( 17 , 18 ). From the vantage point of vaccine research, an outsized role for SIgA in immunity to SARS-CoV-2 would justify investments in intranasal vaccine platforms designed to target mucosal-associated lymphoid tissues and stimulate local humoral (and cellular) responses ( 4 , 19 ).…”