The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
BackgroundThe ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for ...estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making.AimOur objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies.MethodsWe developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT
) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls.ResultsIgG and IgM RBD ELISA, MN and PRNT
were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT
tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test.ConclusionUsing IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT
, is a valid approach for large-scale sero-epidemiology studies.
Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 ...vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.
Surrogate neutralization assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be done without biosafety level 3 containment and in multiple species are desirable. We ...evaluate a recently developed surrogate virus neutralization test (sVNT) in comparison to 90% plaque reduction neutralization tests (PRNT
) in human, canine, cat, and hamster sera. With PRNT
as the reference, sVNT had sensitivity of 98.9% and specificity of 98.8%. Using a panel of immune sera corresponding to other coronaviruses, we confirm the lack of cross-reactivity to other coronaviruses in SARS-CoV-2 sVNT and PRNT
, except for cross-reactivity to SARS-CoV-1 in sVNT.
Limited data exist on antibody responses to mixed vaccination strategies that involve inactivated coronavirus disease 2019 (COVID-19) vaccines, particularly in the context of emerging variants.
We ...conducted an open-label trial of a third vaccine dose of a messenger RNA (mRNA) vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received 2 doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later and tested for antibodies to the ancestral virus using a binding assay (enzyme-linked immunosorbent assay ELISA), a surrogate virus neutralization test (sVNT), and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT.
In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density of 0.3 to 2.2 (P < .001), and mean sVNT levels increased from an inhibition of 17% to 96% (P < .001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose substantially, by 45-fold from day 0 to day 28 against the ancestral virus (P < .001) and by 11-fold against the Omicron variant (P < .001). In daily monitoring, post-vaccination reactions subsided within 7 days for more than 99% of participants.
A third dose of COVID-19 vaccine with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with a well-tolerated safety profile in adults who had received 2 doses of inactivated vaccine 6 months earlier.
NCT05057182.
Abstract
We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity ...and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB,
N
= 116) and CoronaVac (CC,
N
= 123) versus adults after 2 doses of the same vaccine (BB,
N
= 147; CC,
N
= 141) but not in adolescents after 1-dose BNT162b2 (B,
N
= 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents.
•Omicron BA.5 subvariant is now the predominant COVID-19 threat worldwide. While there are some data on pseudovirus neutralization titres to BA.4/5 in comparison to ancestral virus and BA.1 and BA.2 ...variants, live virus plaque neutralization is the definitive method to address this important question.•BA.4 and BA.5 subvariants were less susceptible to BNT162b2 or Coronavac vaccine elicited antibody neutralization than subvariants BA.1, BA.2 and BA.2.12.1. Nevertheless, three doses BNT162b2 or booster of BNT162b2 following two doses of CoronaVac elicited detectable BA.4 and BA.5 neutralizing antibody responses while those vaccinated with three doses of CoronaVac largely fail to do so.•Using live virus neutralization, we see some difference between BA.4 and BA.5 subvariants, with BA.5 being even more immune evasive than BA.4, which may help explain why BA.5 outcompeting BA.4 on the global scale.•We provide data on convalescent BA.5, BA.4 and BA.2.12.1 neutralizing titres in convalescent sera of BA.2 breakthrough infections, which reflects the immune landscape for most of the developed world at the moment, as we face the BA.5 outbreak.•BA.2 breakthrough infections in vaccinated individuals elicited higher levels of BA.4 or BA.5 neutralizing antibody compared to BA.2 infections in vaccine-naïve individuals.
BA.2.12.1, BA.4 and BA.5 subvariants of SARS-CoV-2 variant-of-concern (VOC) Omicron (B.1.1.529) are spreading globally. They demonstrate higher transmissibility and immune escape.
Determine BA.2.12.1, BA.4 and BA.5 virus plaque reduction neutralization test (PRNT) antibody titres in individuals recently vaccinated with BNT162b2 (n=20) or CoronaVac (n=20) vaccines or those convalescent from ancestral wild- type (WT) SARS-CoV-2 (n=20) or BA.2 infections with (n=17) or without (n=7) prior vaccination.
Relative to neutralization of the WT virus, those vaccinated with BNT162b2 had 4.8, 3.4, 4.6, 11.3 and 15.5-fold reductions of geometric mean antibody titres (GMT) to BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 viruses, respectively. Similarly, those vaccinated with CoronaVac had 8.0, 7.0, 11.8, 12.0 and 12.0 fold GMT reductions and those with two doses of CoronaVac boosted by BNT162b2 had 6.1, 6.7, 6,3, 13.0 and 21.2 fold GMT reductions to these viruses, respectively. Vaccinated individuals with BA.2 breakthrough infections had higher GMT antibody levels vs. BA.4 (36.9) and BA.5 (36.9) than unvaccinated individuals with BA.2 infections (BA.4 GMT 8.2; BA.5 GMT 11.0).
BA.4 and BA.5 subvariants were less susceptible to BNT162b2 or CoronaVac vaccine elicited antibody neutralization than subvariants BA.1, BA.2 and BA.2.12.1. Nevertheless, three doses BNT162b2 or booster of BNT162b2 following two doses of CoronaVac elicited detectable BA.4 and BA.5 neutralizing antibody responses while those vaccinated with three doses of CoronaVac largely fail to do so. BA.2 infections in vaccinated individuals led to higher levels of BA.4 or BA.5 neutralizing antibody compared to those who were vaccine-naive.
Contextual Processing in Episodic Future Thought Szpunar, Karl K.; Chan, Jason C. K.; McDermott, Kathleen B.
Cerebral cortex (New York, N.Y. 1991),
07/2009, Letnik:
19, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Remembering events from one's past (i.e., episodic memory) and envisioning specific events that could occur in one's future (i.e., episodic future thought) invoke highly overlapping sets of brain ...regions. The present study employed functional magnetic resonance imaging to test the hypothesis that one source of this shared architecture is that episodic future thought—much like episodic memory—tends to invoke memory for known visual–spatial contexts. That is, regions of posterior cortex (within posterior cingulate cortex PCC, parahippocampal cortex PHC, and superior occipital gyrus SOG) elicit indistinguishable activity during remembering and episodic future thought, and similar regions have been identified as important for establishing visual–spatial contextual associations. In the present study, these regions were similarly engaged when participants thought about personal events in familiar contexts, irrespective of temporal direction (past or future). The same regions, however, exhibited very little activity when participants envisioned personal future events in unfamiliar contextual settings. These findings suggest that regions within PCC, PHC, and SOG support the activation of well-known contextual settings that people tend to imagine when thinking about personal events, whether in the past or future. Hence, this study pinpoints an important similarity between episodic future thought and episodic memory.
Two doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in ...adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data.
With an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored.
A homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified.
The primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.
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