T cell response following anti COVID-19 BNT162b2 vaccination is maintained against the SARS-CoV-2 Omicron B.1.1.529 variant of concern

The progression of the COVID-19 pandemic leads to the emergence of variants of concern (VOC), which may compromise the efficacy of the currently administered vaccines. Antigenic drift can potentially bring about a reduced protective T cell immunity and consequently to more severe disease manifestations. To assess this possibility, the T cell responses to the wild-type, Wuhan-1 SARS-CoV-2 ancestral spike protein and Omicron B.1.1.529 spike protein were compared. Accordingly, peripheral blood mononuclear cells (PBMC) were collected from 8 healthy volunteers 4-5 months following a third vaccination with BNT162b2, and stimulated with overlapping peptide libraries representing the spike of either the ancestral or Omicron SARS-CoV- 2 virus variants. Quantification of the specific T cells was carried out by a fluorescent ELISPOT assay, monitoring interferon-gamma (IFNg), interleukin-10 (IL-10) and interleukin-4 (IL-4) secreting cells. For all the examined individuals, comparable level of reactivity to both forms of spike protein were determined. In addition, a dominant Th1 response was observed, manifested mainly by IFNg secreting cells and only limited numbers of IL-10 and IL-4 secreting cells. The data demonstrates a stable T cell activity to the emerging Omicron variant in the tested individuals, therefore the protective immunity to the variant following BNT162b2 vaccination is not significantly affected.

Durability of Response to a Third BNT162b2 Vaccine in Adults >=60 Years

BackgroundAge/frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older ([≥]65 years) versus younger adults. The durability of response after the third vaccine is unclear. MethodsThis prospective cohort study included healthcare workers/family members[≥]60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10{square}19 (T1), and 74{square}103 (T2) days after the third dose. Anti-spike IgG titers were determined using a commercial assay, seropositivity was defined as[≥]50 AU/mL. Neutralising antibody titres were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. FindingsThe analysis included 97 participants (median age, 70 years [IQR, 66{square}74], 58% CFS level 2). IgG titres, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294{square}923] and 25,429 [14203{square}36114] AU/mL, respectively; p<0{middle dot}001), decreased significantly by T2, but all remained seropositive (median, 8306 AU/mL [IQR, 4595{square}14701], p<0{middle dot}001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (p=0{middle dot}004). At T2, 60 patients were evaluated for neutralising antibodies; all were seropositive (median, 1294 antibody titre [IQR, 848{square}2072]). Neutralising antibody and anti-spike IgG levels were correlated (R=0{middle dot}6, p<0{middle dot}001). No major adverse events or COVID-19 infections were reported. InterpretationAnti-spike IgG and neutralising antibody levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults[≥]60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority. FundingNo external funding. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed on Aug 1, 2021, for published research articles with no date restrictions, using the search terms of "SARS-Cov-2", "COVID-19", "vaccine", "dose", "antibody response", and "adults" with English as a filter. Several studies were identified that investigated waning of immunity in healthy adults. It is well established through epidemiology and serology studies that in healthy adults, the protection conferred by the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer/BioNtech) wanes significantly after several months. Studies have also shown that the immune response to the vaccine varies with age, and that after the second dose of the BNT162b2 vaccine, the older adult population (65-85 years of age) typically has a lower immune response (as reflected in an analysis of anti-spike IgG antibodies and neutralising antibody titres), than younger adults (18-55 years of age), and that the immunity wanes in all age groups within several months. Added value of this studyThis is, to our knowledge, the first study that examined anti-spike IgG and neutralising antibody titres three months after the third BNT162b2 vaccine dose. The study has demonstrated that three months after that dose, participants, who were healthy adults aged 60 years and older, remained anti-spike IgG seropositive, although a significant decrease in anti-spike IgG titres was observed (compared to two weeks after the third dose). In addition, a statistically significant correlation was observed between the neutralising antibody titres and the anti-spike IgG titres, and all participants were seropositive for neutralising antibodies three months after the third dose. Also, no major adverse events or COVID-19 infections were reported. Implications of all the available evidenceAs our data suggest that a third dose of the BNT162b2 vaccine is effective in maintaining adequate immune response against COVID-19 for at least several months in healthy adults aged 60 years and older, and as it is well established that older adults are at higher risk of severe COVID-19 disease and COVID-19 mortality, providing a third dose to this population should be a top priority. Our data also highlight that understanding the waning of the immune response in other age groups is key for making evidence-based policies regarding booster vaccinations for the population at large.

Nonclinical Safety and Immunogenicity of an rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs

rVSV-{Delta}G-SARS-CoV-2-S is a clinical stage (Phase 2) replication competent recombinant vaccine against SARS-CoV-2. Nonclinical safety, immunogenicity and efficacy studies were conducted in 4 animal species, using multiple dose levels (up to 108 PFU/animal) and various dosing regimens. There were no treatment related mortalities in any study, or any noticeable clinical signs. Compared to unvaccinated controls, hematology and biochemistry parameters were unremarkable and no adverse histopathological findings gave cause for safety concern in any of the studies. There was no viral shedding in urine, nor viral RNA detected in whole blood or serum samples 7 days post vaccination. The rVSV-{Delta}G-SARS-CoV-2-S vaccine immune response gave rise to neutralizing antibodies, cellular immune response, and increased lymphocytic cellularity in the spleen germinal centers and regional lymph node. No evidence for neurovirulence was found in C57BL/6 immune competent mice or in highly sensitive IFNAR KO mice. Vaccine virus replication and distribution in K18 hACE2 transgenic mice showed a gradual clearance from the vaccination site with no vaccine virus recovered from the lungs. The rVSV-{Delta}G-SARS-CoV-2-S vaccine was well tolerated locally and systemically and elicited an effective immunogenic response up to the highest dose tested, supporting further clinical development.

Design of SARS-CoV-2 RBD mRNA Vaccine Using Novel Ionizable Lipids

The novel coronavirus SARS-CoV-2 has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple and rapid platform for immunization, and therefore have been employed in recent studies towards the development of a SARS-CoV-2 vaccine. In this study, we present the design of a lipid nanoparticles (LNP)-encapsulated receptor binding domain (RBD) mRNA vaccine. Several ionizable lipids have been evaluated in vivo in a luciferase mRNA reporter assay, and two leading LNPs formulation have been chosen for the subsequent RBD mRNA vaccine experiment. Intramuscular administration of LNP RBD mRNA elicited robust humoral response, high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. These novel lipids open new avenues for mRNA vaccines in general and for a COVID19 vaccine in particular.