Abstract Data about the duration of humoral response following COVID-19 vaccines are mandatory to establish appropriate population vaccination strategy. This study reports on the antibody decline observed in a population of COVID-19 naïve and COVID-19 positive individuals having received the two dose regimen of the BNT162b2 vaccine. Six months after vaccination, a significant antibody decline was observed in both COVID-19 naïve and positive individuals. The estimated half-life of total and IgG antibodies differs and ranges from several months for total antibodies to only several weeks for IgG antibodies, explaining the significant proportions of participants with non-detectable levels of neutralizing antibodies at 6 months. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus will require appropriate clinical studies. Nevertheless, these data are already important to support the decision-making on the potential use of a booster dose.
Abstract Evidence about the long‐term persistence of the booster‐mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID‐19 naive and 51 with a history of SARS‐CoV‐2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2‐ and 11.5‐fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS‐CoV‐2 infection. A corresponding 2.5‐ and 2.9‐fold decrease in binding antibodies was observed. The estimated T 1/2 of neutralizing antibodies in participants with and without history of SARS‐CoV‐2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T 1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE ( r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era.
Abstract Studies about the evaluation of the humoral and cellular response following the bivalent booster administration are still scarce. The aim of this study was to assess the humoral and cellular response in a cohort of healthcare workers that received either the BA.1 or the BA.4/5 bivalent booster.Blood samples from participants were collected before the administration of either the BA.1 or BA.4/5 bivalent booster from Pfizer-BioNTech and after 14, 28, and 90 days. The humoral response was evaluated using neutralizing antibodies against the BA.5 Omicron variant and binding total and IgG antibodies. The cellular response was assessed by measurement of the release of interferon gamma (IFNγ) from T cells in response to an in vitro SARS-CoV-2 stimulation.Although most participants still had a robust cellular response before the booster, a significant increase in the cellular response was observed after 2 weeks, especially in participants presenting lower levels of IFNγ before the booster administration. Levels of IFNγ remained stable at 3 months and contrast sharply with the rapid decrease of BA.5-specific neutralizing antibodies. Binding antibodies were only modestly correlated to the neutralizing capacity. The evolution of the humoral and cellular response was non-significantly different between participants that received the BA.1 or the BA.4/5 bivalent booster. The monitoring of the humoral and cellular response could be useful to identify patients with a poor adapted immunity that would need to benefit first from an additional booster shot.
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Abstract The diagnostic of SARS-CoV-2 infection relies on reverse transcriptase polymerase chain reactions (RT-PCR) performed on nasopharyngeal (NP) swabs. Nevertheless, false negative results can be obtained with inadequate sampling procedures making the use of other matrices of interest. This study aims at evaluating the kinetic of serum N antigen in severe and non-severe patients and compare the clinical performance of serum antigenic assays with NP RT-PCR. Ninety patients were included and monitored for several days. Disease severity was determined according to the WHO clinical progression scale. The serum N antigen was measured with a chemiluminescent assay (CLIA) and the Single Molecular Array (Simoa). Thresholds for severity were determined. In severe patients, the peak antigen response was observed 7 days after the onset of symptoms followed by a decline. No peak response was observed in non-severe patients. Severity threshold for the Simoa and the CLIA provided positive likelihood ratio of 30.0 and 10.9 for the timeframe between day 2 and day 14, respectively. Compared to NP RT-PCR, antigenic assays were able to discriminate the severity of the disease (p = 0.0174, 0.0310 and p = 0.1551 with the Simoa, the CLIA and the NP RT-PCR, respectively). Sensitive N antigen detection in serum thus provides a valuable new marker for COVID-19 diagnosis and evaluation of disease severity. When assessed during the first 2 weeks since the onset of symptoms, it may help in identifying patients at risk of developing severe COVID-19 to optimize better intensive care utilization.
Some studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable.
Background: The detection of neutralizing anti-SARS-CoV-2 antibodies is important since they represent the subset of antibodies able to prevent the virus to invade human cells. The aim of this study is to evaluate the clinical performances of an in-house pseudovirus neutralization test (pVNT) versus a commercial surrogate neutralization test (sVNT). Material and Methods: A total of 114 RT-PCR positives samples from 75 COVID-19 patients were analyzed using a pVNT and an sVNT technique. Fifty-six pre-pandemic samples were also analyzed to assess the specificity of the two techniques. An analysis of the repeatability and the reproducibility of the pVNT was also performed. Results: A coefficient of variation (CV) of 10.27% for the repeatability of the pVNT was computed. For the reproducibility test, CVs ranged from 16.12% for low NAbs titer to 6.40% for high NAbs titer. Regarding the clinical sensitivity, 90 RT-PCR positive samples out of 114 were positive with the pVNT (78.94%), and 97 were positive with the sVNT (84.21%). About the clinical specificity, all 56 pre-pandemic samples were negative in both techniques. When comparing the sVNT to the pVNT, the specificity and sensibility were 66.67% (95%CI: 47.81–85.53%) and 98.88% (95%CI: 96.72–99.99%), respectively. Conclusions: The results obtained with the automated sVNT technique are consistent with those obtained with the pVNT technique developed in-house. The results of the various repeatability and reproducibility tests demonstrate the good robustness of the fully manual pVNT technique.
IntroductionAn increase evasion of the SARS-CoV-2 virus towards vaccination strategies and natural immunity has been rapidly described notably due to mutations in the spike receptor binding domain and the N-terminal domain.Material and methodsParticipants of the CRO-VAX HCP study who received the bivalent booster were followed at 6 months. A pseudovirus‐neutralization test was used to assess the neutralization potency of antibodies against D614G, Delta, BA.1, BA.5, XBB.1.5, BA.2.86, FL.1.5.1, and JN-1.ResultsThe neutralizing capacity of antibodies against Omicron variant or subvariants was significantly reduced compared to D614G and Delta (p<0.0001). The lowest neutralizing response that was observed with JN-1 (GMT=22.1) was also significantly lower compared to XBB.1.5 (GMT=29.5, p<0.0001), BA.2.86 (GMT=29.6, p<0.0001), and FL.1.5.1 (GMT=25.2, p<0.0001). Participants that contracted a breakthrough infection due to XBB.1.5 had significantly higher neutralizing antibodies against all variants compared to uninfected participants, especially against Omicron variant and subvariants.ConclusionOur results confirm that JN.1 is one of the most immune evading variants to date and that the BA.2.86 subvariant did not show an increased immunity escape compared to XBB.1.5. The stronger response in BKI with Omicron variant and subvariants supports the need to use vaccine antigens that target circulating variants.
