Background Understanding immunogenicity and effectiveness of SARS-CoV-2 vaccines is critical to guide rational use. Methods We compared the immunogenicity of mRNA-1273, BNT-162b2 or Ad26.COV2.S in healthy ambulatory adults in Massachusetts, USA. To correlate immunogenicity with effectiveness of the three vaccines, we performed an inverse-variance meta-analysis of population level effectiveness from public health reports in >40 million individuals. Results A single dose of either mRNA vaccine yielded comparable antibody and neutralization titers to convalescent individuals. Ad26.COV2.S yielded lower antibody concentrations and frequently undetectable neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients. Regardless of vaccine, <50% of vaccinees demonstrated CD8+ T-cell responses. Antibody concentrations and neutralization titers increased comparably after the first dose of either vaccine, and further in recipients of a second dose. Prior infection was associated with high antibody concentrations and neutralization even after a single dose and regardless of vaccine. Neutralization of beta, gamma and delta strains were poorer regardless of vaccine. In meta-analysis, relative to mRNA1273 the effectiveness of BNT162b2 was lower against infection and hospitalization; and Ad26COV2.S was lower against infection, hospitalization and death. Conclusions Variation in the immunogenicity correlates with variable effectiveness of the three FDA EUA vaccines deployed in the USA.
PURPOSE The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood. METHODS We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti–SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison. RESULTS Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] 2.9, log10 geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; P < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses ( P < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type ( P < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses ( P = .002 for concentration, P = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose). CONCLUSION Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.
Patients with cancer are more likely to have impaired immune responses to SARS-CoV-2 vaccines. We study the breadth of responses against SARS-CoV-2 variants after primary vaccination in 178 patients with a variety of tumor types and after booster doses in a subset. Neutralization of alpha, beta, gamma, and delta SARS-CoV-2 variants is impaired relative to wildtype, regardless of vaccine type. Regardless of viral variant, mRNA1273 is the most immunogenic, followed by BNT162b2, and then Ad26.COV2.S. Neutralization of more variants (breadth) is associated with a greater magnitude of wildtype neutralization, and increases with time since vaccination; advancing age associates with a lower breadth. The concentrations of anti-spike protein antibody are a good surrogate for breadth (positive predictive value of =90% at >1,000 U/mL). Booster SARS-CoV-2 vaccines confer enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with the current vaccines increases the breadth of responses against variants.
Background: Understanding variation in immunogenicity may help rationalize use of existing SARS-CoV-2 vaccines. Methods: We compared immune responses in ambulatory adults vaccinated with mRNA-1273 , BNT-162b2 or Ad26.COV2.S in Massachusetts, USA between February and May 2021. Control groups were pre-pandemic controls (n=1220) and individuals without (n=112) or with prior SARS-CoV-2 infection (n=130) sampled in mid-2020. We measured total anti-spike IgG/M/A antibodies (Roche Elecsys Anti-SARS-COV-2 S assay), anti-receptor-binding-domain (RBD) antibodies; neutralization of SARS-CoV-2 pseudovirus; and T-cell responses. Findings In individuals with prior infection, all vaccines were associated with higher antibody concentrations and neutralization than those in convalescent individuals, even after a single dose. In individuals without prior infection, a single dose of either mRNA vaccine yielded comparable concentrations and neutralization to convalescent unvaccinated individuals, and Ad26.COV2.S yielded lower antibody concentrations and neutralization titers. The second dose of either mRNA vaccine boosted responses. At a median of 24 days after vaccination, two of 21 (9.5%) Ad26.COV2.S recipients had a neutralization titer higher than pre-pandemic controls; repeat sampling at a median 66 days after vaccination found most (11/15 (73%) remained negative. Antibody concentrations and neutralization titers increased similarly after the first dose of either vaccine, and even further in recipients of a second dose of vaccine. T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients. Interpretation SARS-CoV-2 vaccines vary significantly in immunogenicity in individuals without prior infection. If confirmed in effectiveness studies, public health policy may need to be tailored to each vaccine, or even individual responses.
ABSTACT The rapid worldwide spread of severe acute respiratory system coronavirus 2 (SARSCoV-2) infection has propelled the rapid development of serological tests that can detect anti-SARS-CoV-2 antibodies. These have been used for studying the prevalence and spread of infection in different populations, helping establish a recent diagnosis of coronavirus disease 2019 (COVID-19), and will likely be used to confirm humoral immunity after infection or vaccination. However, nearly all lab-based high-throughput SARS-CoV-2 serological assays require a serum sample from venous blood draw, limiting their applications and scalability. Here, we present a method that enables large scale SARS-CoV-2 serological studies by combining self or office collection of fingerprick blood with a volumetric absorptive microsampling device (Mitra, Neoteryx, LLC) with a high-throughput electrochemiluminescence-based SARS-CoV-2 total antibody assay (Roche Elecsys, Roche Diagnostics, Inc.) that is emergency use authorization (EUA) approved for use on serum samples and widely used by clinical laboratories around the world. We found that the Roche Elecsys assay has a high dynamic range that allows for accurate detection of SARS-CoV-2 antibodies in serum samples diluted 1:20 as well as contrived dried blood extracts. Extracts of dried blood from Mitra devices acquired in a community seroprevalence study showed near identical sensitivity and specificity in detection of SARS-CoV-2 antibodies as compared to neat sera using predefined thresholds for each specimen type. Overall, this study affirms the use of Mitra dried blood collection device with the Roche Elecsys SARS-CoV-2 total antibody assay for remote or at-home testing as well as large-scale community seroprevalence studies.
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