Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 228
N Engl J Med ; 388(21): e76, 2023 May 25.
Article in English | MEDLINE | ID: covidwho-20242186

COVID-19 , Humans
Sci Transl Med ; 14(629): eabj5305, 2022 Jan 26.
Article in English | MEDLINE | ID: covidwho-2325160


Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.

Aluminum Hydroxide , COVID-19 , Aged , Animals , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , Humans , Mice , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
N Engl J Med ; 388(19): e72, 2023 May 11.
Article in English | MEDLINE | ID: covidwho-2318744
Open Forum Infect Dis ; 9(8): ofac417, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2319246


Background: Patients with lymphoid malignancies are at risk for poor coronavirus disease 2019 (COVID-19)-related outcomes and have reduced vaccine-induced immune responses. Currently, a 3-dose primary regimen of mRNA vaccines is recommended in the United States for immunocompromised hosts. Methods: A prospective cohort study of healthy adults (n = 27) and patients with lymphoid malignancies (n = 94) was conducted, with longitudinal follow-up through completion of a 2- or 3-dose primary mRNA COVID vaccine series, respectively. Humoral responses were assessed in all participants, and cellular immunity was assessed in a subset of participants. Results: The rate of seroconversion (68.1% vs 100%) and the magnitude of peak anti-S immunoglobulin G (IgG) titer (median anti-S IgG = 32.4, IQR = 0.48-75.0 vs median anti-S IgG = 72.6, IQR 51.1-100.1; P = .0202) were both significantly lower in patients with lymphoid malignancies compared to the healthy cohort. However, peak titers of patients with lymphoid malignancies who responded to vaccination were similar to healthy cohort titers (median anti-S IgG = 64.3; IQR, 23.7-161.5; P = .7424). The third dose seroconverted 7 of 41 (17.1%) patients who were seronegative after the first 2 doses. Although most patients with lymphoid malignancies produced vaccine-induced T-cell responses in the subset studied, B-cell frequencies were low with minimal memory cell formation. Conclusions: A 3-dose primary mRNA series enhanced anti-S IgG responses to titers equivalent to healthy adults in patients with lymphoid malignancies who were seropositive after the first 2 doses and seroconverted 17.1% who were seronegative after the first 2 doses. T-cell responses were present, raising the possibility that the vaccines may confer some cell-based protection even if not measurable by anti-S IgG.

N Engl J Med ; 387(16): e47, 2022 10 20.
Article in English | MEDLINE | ID: covidwho-2310702

COVID-19 , Humans , SARS-CoV-2
N Engl J Med ; 386(17): e53, 2022 04 28.
Article in English | MEDLINE | ID: covidwho-2310701
N Engl J Med ; 387(23): e73, 2022 12 08.
Article in English | MEDLINE | ID: covidwho-2310698

COVID-19 , Health Equity , Humans
N Engl J Med ; 388(15): e64, 2023 Apr 13.
Article in English | MEDLINE | ID: covidwho-2302798
Sci Transl Med ; 15(692): eade9078, 2023 04 19.
Article in English | MEDLINE | ID: covidwho-2292152


The best assay or marker to define mRNA-1273 vaccine-induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antibodies to the spike protein (spike IgG) or receptor binding domain (RBD IgG) and pseudovirus neutralizing antibody 50 or 80% inhibitory dilution titer measured on day 29 or day 57, as correlates of risk (CoRs) and CoPs against symptomatic COVID-19 over 4 months after dose. Here, we assessed a new marker, live virus 50% microneutralization titer (LV-MN50), and compared and combined markers in multivariable analyses. LV-MN50 was an inverse CoR, with a hazard ratio of 0.39 (95% confidence interval, 0.19 to 0.83) at day 29 and 0.51 (95% confidence interval, 0.25 to 1.04) at day 57 per 10-fold increase. In multivariable analyses, pseudovirus neutralization titers and anti-spike binding antibodies performed best as CoRs; combining antibody markers did not improve correlates. Pseudovirus neutralization titer was the strongest independent correlate in a multivariable model. Overall, these results supported pseudovirus neutralizing and binding antibody assays as CoRs and CoPs, with the live virus assay as a weaker correlate in this sample set. Day 29 markers performed as well as day 57 markers as CoPs, which could accelerate immunogenicity and immunobridging studies.

2019-nCoV Vaccine mRNA-1273 , COVID-19 , Humans , Vaccine Efficacy , COVID-19/prevention & control , Antibodies, Neutralizing , Immunoglobulin G , Antibodies, Viral
Transplant Cell Ther ; 29(6): 398.e1-398.e5, 2023 06.
Article in English | MEDLINE | ID: covidwho-2290940


Patients receiving chimeric antigen receptor T cell (CAR-T) therapy may have impaired humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations owing to their underlying hematologic malignancy, prior lines of therapy, and CAR-T-associated hypogammaglobulinemia. Comprehensive data on vaccine immunogenicity in this patient population are limited. A single-center retrospective study of adults receiving CD19 or BCMA-directed CAR-T therapy for B cell non-Hodgkin lymphoma or multiple myeloma was conducted. Patients received at least 2 doses of SARS-CoV-2 vaccination with BNT162b2 or mRNA-1273 or 1 dose of Ad26.COV2.S and had SARS-CoV-2 anti-spike antibody (anti-S IgG) levels measured at least 1 month after the last vaccine dose. Patients were excluded if they received SARS-CoV-2 monoclonal antibody therapy or immunoglobulin within 3 months of the index anti-S titer. The seropositivity rate (assessed by an anti-S assay cutoff of ≥.8 U/mL in the Roche assay) and median anti-S IgG titers were analyzed. Fifty patients were included in the study. The median age was 65 years (interquartile range [IQR], 58 to 70 years), and the majority were male (68%). Thirty-two participants (64%) had a positive antibody response, with a median titer of 138.5 U/mL (IQR, 11.61 to 2541 U/mL). Receipt of ≥3 vaccines was associated with a significantly higher anti-S IgG level. Our study supports current guidelines for SARS-CoV-2 vaccination among recipients of CAR-T therapy and demonstrates that a 3-dose primary series followed by a fourth booster increases antibody levels. However, the relatively low magnitude of titers and low percentage of nonresponders demonstrates that further studies are needed to optimize vaccination timing and determine predictors of vaccine response in this population.

COVID-19 , Receptors, Chimeric Antigen , Aged , Female , Humans , Male , Middle Aged , Ad26COVS1 , Antibodies, Viral , BNT162 Vaccine , Cell- and Tissue-Based Therapy , COVID-19/prevention & control , COVID-19 Vaccines , Immunogenicity, Vaccine , Immunoglobulin G , Receptors, Chimeric Antigen/therapeutic use , Retrospective Studies , SARS-CoV-2
Clin Infect Dis ; 2023 Apr 10.
Article in English | MEDLINE | ID: covidwho-2292557


In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines.

N Engl J Med ; 388(11): e39, 2023 Mar 16.
Article in English | MEDLINE | ID: covidwho-2278952
Clin Biochem ; 117: 60-68, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2284244


BACKGROUND: Serologic assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proposed to assist with the acute diagnosis of infection, support epidemiological studies, identify convalescent plasma donors, and evaluate vaccine response. METHODS: We report an evaluation of nine serologic assays: Abbott (AB) and Epitope (EP) IgG and IgM, EUROIMMUN (EU) IgG and IgA, Roche anti-N (RN TOT) and anti-S (RS TOT) total antibody, and DiaSorin (DS) IgG. We evaluated 291 negative controls (NEG CTRL), 91 PCR positive (PCR POS) patients (179 samples), 126 convalescent plasma donors (CPD), 27 healthy vaccinated donors (VD), and 20 allogeneic hematopoietic stem cell transplant (HSCT) recipients (45 samples). RESULTS: We observed good agreement with the method performance claims for specificity (93-100%) in NEG CTRL but only 85% for EU IgA. The sensitivity claims in the first 2 weeks of symptom onset was lower (26-61%) than performance claims based on > 2 weeks since PCR positivity. We observed high sensitivities (94-100%) in CPD except for AB IgM (77%), EP IgM (0%). Significantly higher RS TOT was observed for Moderna vaccine recipients then Pfizer (p-values < 0.0001). A sustained RS TOT response was observed for the five months following vaccination. HSCT recipients demonstrated significantly lower RS TOT than healthy VD (p < 0.0001) at dose 2 and 4 weeks after. CONCLUSIONS: Our data suggests against the use of anti-SARS-CoV-2 assays to aid in acute diagnosis. RN TOT and RS TOT can readily identify past-resolved infection and vaccine response in the absence of native infection. We provide an estimate of expected antibody response in healthy VD over the time course of vaccination for which to compare antibody responses in immunosuppressed patients.

COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , Sensitivity and Specificity , Antibodies, Viral , Immunoglobulin G , COVID-19 Serotherapy , Immunoglobulin M , Immunoglobulin A , COVID-19 Testing