Receptor-binding Domain Antibodies Research Articles

Metrics from Wearable Devices as Candidate Predictors of Antibody Response Following Vaccination against COVID-19: Data from the Second TemPredict Study.

There is significant variability in neutralizing antibody responses (which correlate with immune protection) after COVID-19 vaccination, but only limited information is available about predictors of these responses. We investigated whether device-generated summaries of physiological metrics collected by a wearable device correlated with post-vaccination levels of antibodies to the SARS-CoV-2 receptor-binding domain (RBD), the target of neutralizing antibodies generated by existing COVID-19 vaccines. One thousand, one hundred and seventy-nine participants wore an off-the-shelf wearable device (Oura Ring), reported dates of COVID-19 vaccinations, and completed testing for antibodies to the SARS-CoV-2 RBD during the U.S. COVID-19 vaccination rollout. We found that on the night immediately following the second mRNA injection (Moderna-NIAID and Pfizer-BioNTech) increases in dermal temperature deviation and resting heart rate, and decreases in heart rate variability (a measure of sympathetic nervous system activation) and deep sleep were each statistically significantly correlated with greater RBD antibody responses. These associations were stronger in models using metrics adjusted for the pre-vaccination baseline period. Greater temperature deviation emerged as the strongest independent predictor of greater RBD antibody responses in multivariable models. In contrast to data on certain other vaccines, we did not find clear associations between increased sleep surrounding vaccination and antibody responses.

Neutralizing antibody activity against the B.1.617.2 (delta) variant 8 months after two-dose vaccination with BNT162b2 in health care workers

ObjectivesHumoral immunity wanes over time after two-dose BNT162b2 vaccination. Emerging variants of concern, such as the B.1.617.2 (delta) variant, are increasingly responsible for breakthrough infections owing to their higher transmissibility and partial immune escape. Longitudinal data on neutralization against the B.1.617.2 (delta) variant are urgently needed to guide vaccination strategies. MethodsIn this prospective longitudinal observational study, anti-S1 IgG and surrogate neutralizing antibodies were measured in 234 collected samples from 60 health care workers after two-dose vaccination with BNT162b2 at five different time points over an 8-month period. In addition, antibodies against various severe acute respiratory syndrome coronavirus 2 epitopes, neutralization against wild-type, and cross-neutralization against the B.1.617.2 (delta) variant using a live virus assay were measured 6 weeks (second time point) and 8 months (last time point) after first vaccine dose. ResultsMedian (interquartile range) anti-S1 IgG, surrogate neutralizing, and receptor-binding domain antibodies decreased significantly from a maximum level of 147 (102–298), 97 (96–98), and 20 159 (19 023–21 628) to 8 (4–13), 92 (80–96), and 15 324 (13 055–17 288) at the 8-month follow-up, respectively (p < 0.001 for all). Neutralization against the B.1.617.2 (delta) variant was detectable in all 36 (100%) participants at 6 weeks and in 50 of 53 (94%) participants 8 months after first vaccine dose. Median (interquartile) ID50 as determined by a live virus assay decreased from 160 (80–320) to 40 (20–40) (p < 0.001). DiscussionAlthough humoral immunity wanes over time after two-dose BNT162b2 vaccination in healthy individuals, most individuals still had detectable neutralizing activity against the B.1.617.2 (delta) variant after 8 months.

Antibody Course and Memory B-Cell Response in the First Year After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BackgroundThe possibility of repeat infections with SARS-CoV-2 raises questions regarding quality and longevity of the virus-induced immune response.MethodsThe antibody course and memory B-cell (MBC) response against SARS-CoV-2 proteins, influenza virus nucleoprotein (NP) and tetanus toxin (Ttx) were examined in adults with mild to moderate SARS-CoV-2 infection in the first year after infection.ResultsThe concentration of SARS-CoV-2 RBD-specific antibodies was low compared with the concentration of influenza virus NP-specific antibodies. The SARS-CoV-2 RBD antibody half-life increased from 95 days in the first six months to 781 days after 9-12 months. The SARS-CoV-2 NP antibody half-life increased from 88 to 248 days. Two thirds of the subjects had SARS CoV-2-specific MBC responses 12 months after infection. SARS-CoV-2 antibody levels correlated with the MBC frequency at 12 months.ConclusionsThe low concentration of SARS-CoV-2 spike protein antibodies indicates that re-exposure to the virus or vaccination are required to use the B-cell immunity to full capacity. The existence of a robust SARS CoV-2 MBC response at 12 months in most subjects and the substantially increasing antibody half-life provide evidence that the immune response is developing into long-term immunity. The early antibody reaction and the ensuing MBC response are interdependent.

Persistence of immunogenicity, contributing factors of an immune response, and reactogenicities after a single dose of the ChAdOx1 (AZD1222) COVID-19 vaccine in the Thai population

ABSTRACT Introduction Due to the vaccine’s short supply and the efficacy of a single dose of the ChAdOx1 (AZD1222) vaccine, many governments delayed the interval between prime and boost dose from 4 to 8–12 weeks. However, the waning of immune response in this period is a concern. This study evaluated the durability, contributing factors of anti-RBD antibody concentration, and reactogenicities after the single dose of AZD1222 vaccine in the Thai population. Methods This was a single-center, prospective cohort study at Chulabhorn Hospital, Bangkok, Thailand. Individuals 18 years or older who were negative for anti-SARS-CoV-2 antibody were eligible. Anti- receptor-binding domain antibody concentrations were tested at least three weeks after the first vaccination and immediately before the second dose of vaccine. Information on reactogenicities was obtained via a questionnaire sent by a short message service. Results Anti-RBD Antibody concentration at 2 and 3 months post-vaccination were significantly higher than at 1 months post-vaccination (20.14 BAU/mL (95%CI; 16.37, 24.77) at 1 month, 48.08 BAU/mL (95%CI; 42.76, 54.08) at 2 month, and 65.01 BAU/mL (95%CI; 58.88,71.61) at 3 month). Adverse events occurred in approximately 60% of participants. Factors influencing vaccine immunogenicity include age, sex, the time elapsed from the first dose of vaccine, and underlying disease with diabetes and hematologic disease. Conclusion A single dose of AZD1222 could elicit immune responses that did not decline within three months in Thai individuals. These data support the public health strategy of a delay between the prime and boost dose of AZD1222 of 4 to 12 weeks.

OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients

BackgroundAntibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody.Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination.MethodsAnti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine.ResultsAnti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 – 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2).There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumab-treated patients after one or two doses of either vaccine.Antibody half-life was shorter in infliximab- than vedolizumab-treated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 – 4.1] vs 7.2 weeks [95% CI 6.8 – 7.6]) and ChAdOx1 nCoV-19 (5.3 weeks [95% CI 5.1 – 5.5] vs 9.3 weeks [95% CI 8.5 – 10.2], p value < 0.0001).Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3).Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 – 0.99], p = 0.035). ConclusionInfliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.

SARS-CoV-2 mRNA vaccine induces robust specific and cross-reactive IgG and unequal neutralizing antibodies in naive and previously infected people

Understanding vaccine-mediated protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to overcoming the global coronavirus disease 2019 (COVID-19) pandemic. We investigate mRNA-vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three time points: before vaccination, after the first dose, and after the second dose. Following complete vaccination, both naive and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses. However, the strength and frequency of SARS-CoV-2 neutralizing antibodies in naive individuals were lower than in previously infected individuals. After the first vaccine dose, one-third of previously infected individuals lacked neutralizing antibodies; this was improved to one-fifth after the second dose. In all individuals, neutralizing antibody responses against the Alpha and Delta variants were weaker than against the reference strain. Our findings support future tailored vaccination strategies against emerging SARS-CoV-2 variants as mRNA-vaccine-induced neutralizing antibodies are highly variable among individuals.

Heterologous prime-boost with the mRNA-1273 vaccine among CoronaVac-vaccinated healthcare workers in Indonesia.

PurposeThis study was performed to investigate humoral immune response and adverse events upon the heterologous prime-boost with a single dose of the mRNA-1273 vaccine among fully CoronaVac-vaccinated, infection-naïve healthcare workers in Indonesia.Materials and MethodsOne hundred twenty-five eligible healthcare workers were recruited from one hospital for this prospective cohort study. Blood collection was conducted twice, i.e., on 7 days before and 28 days after the booster vaccination. The titer of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies was quantified accordingly. The post-vaccination adverse event was recorded for both CoronaVac and mRNA-1273 vaccinations. Any breakthrough infection was monitored during the follow-up period. Wilcoxon matched-pairs signed rank test was used to test differences between groups.ResultsA significant increase was observed in the titer of anti-SARS-CoV-2 RBD antibodies upon receiving the mRNA-1273 booster (geometric mean titers of 65.57 and 47,445 U/mL in pre- and post-booster, respectively), supporting the argument to use heterologous prime-boost vaccination to improve the protection against COVID-19 in a high-risk population. The mRNA-1273 vaccine, however, caused a higher frequency of adverse events than the CoronaVac vaccine. Nonetheless, the adverse events were considered minor medical events and temporary as all subjects were not hospitalized and fully recovered. Of note, no breakthrough infection was observed during the follow-up to 12 weeks post-booster.ConclusionThe heterologous prime-boost vaccination of healthcare workers with a single dose of the mRNA-1273 vaccine generated a significant elevation in humoral immune response towards RBD of SARS-CoV-2 and was associated with a higher frequency, but minor and transient, adverse events.

Assessment on anti-SARS-CoV-2 receptor-binding domain antibodies among CoronaVac-vaccinated Indonesian adults.

The immunogenicity of CoronaVac among Indonesian adults at the academic premises was investigated. Two doses of CoronaVac vaccine induced a complete seroconversion on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) naïve adults with titers of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies ranging from 9.1 to 151.9 U/mL. The median value was lower than the one observed in recovered adults with mild coronavirus disease 2019 (38.7 vs. 114.5 U/mL). Nonetheless, 93.6% of the vaccinated adults, in contrast to 76.5% of the recovered adults, displayed inhibition rates above the cut-off to block RBD-angiotensin-converting enzyme 2 binding. This suggests that two doses of CoronaVac were immunogenic and likely to be protective among Indonesian adults.

A scalable serology solution for profiling humoral immune responses to SARS‐CoV‐2 infection and vaccination

ObjectivesAntibody testing against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been instrumental in detecting previous exposures and analyzing vaccine‐elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS‐CoV‐2 antibodies, discriminate between natural infection‐ and vaccination‐induced responses, and assess antibody‐mediated inhibition of the spike‐angiotensin converting enzyme 2 (ACE2) interaction.MethodsWe developed methods and reagents to detect SARS‐CoV‐2 antibodies by enzyme‐linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2‐spike or ‐RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard.ResultsOur single‐point IgG‐based ELISAs accurately distinguished non‐infected and infected individuals. For seroprevalence assessment (in a non‐vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti‐spike and ‐RBD (but not ‐N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability.ConclusionsMeasuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike‐ACE2 interactions in high‐throughput enables large‐scale analyses of humoral immune responses to SARS‐CoV‐2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter‐laboratory data comparison and aggregation.

Insights from computational analysis: how does the SARS-CoV-2 Delta (B.1.617.2) variant hijack ACE2 more effectively?

The SARS-CoV-2 Delta (B.1.617.2) variant was identified in India in October 2020, and it has quickly become the mainstream strain with strong toxicity and spread, posing great challenges to epidemic control. However, the molecular mechanism of its powerful infectivity remains unclear. It is meaningful to investigate the process of Delta variant's receptor-binding domain (RBD) binding to angiotensin-converting enzyme 2 (ACE2). Here, we performed three repeated molecular dynamics simulations for each system to avoid accidents, and the alanine scanning combined with the interaction entropy (ASIE) method was utilized to evaluate the binding free energy. Through the detailed energy and conformational analysis, the binding mechanism of the Delta variant was illustrated. The results showed that the existence of L452R and T478K mutations can trigger the effective hijacking of ACE2 by the Delta variant through the following three ways: (i) these two mutations can significantly enhance the electrostatic energy of the system by the introduction of two positively charged amino acids (Arg and Lys), thereby increasing the binding affinity of RBD and ACE2, (ii) the Loops 1, 3, and 4 in the receptor-binding motif (RBM) of RBD form a tighter conformation under the dominance of the T478K mutation, allowing ACE2 to be captured more effectively than the wild-type system, and (iii) these conformational changes lead to a more stable hydrogen bond in the Delta variant, which further ensures the stability of the binding. In addition, to explore the effect of mutations on the antibody, the key residues contributing to the changes in the binding ability of RBD in the Delta variant with the existing 42 neutralizing monoclonal antibodies (mAbs) have been preliminarily evaluated. The present study reveals the molecular mechanism for the increased infectivity of SARS-CoV-2 caused by mutations, and the key sites that cause antigenic changes were screened. It provides important theoretical insights for the development of novel targeted RBD drugs and antibodies.

Reactogenicity and Immunogenicity of the ChAdOx1 nCOV-19 Coronavirus Disease 2019 Vaccine in South Korean Healthcare Workers.

The association between reactogenicity and immunogenicity of the ChAdOx1 nCOV-19 is controversial. We aimed to evaluate this association among South Korean healthcare workers (HCWs). Participants received two doses of the ChAdOx1vaccine 12 weeks apart. Blood samples were tested for anti-severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) spike protein receptor binding domain antibodies about 2 months after the first and second doses using the Elecsys Anti-SARS-CoV-2 S assay kits. Adverse events were noted using an online self-reporting questionnaire. Among the 232 HCWs, pain (85.78% after the first dose vs. 58.62% after the second dose, p<0.001) was the most prominent local reaction, and myalgia or fatigue (84.05% vs. 53.02%, p<0.001) was the most prominent systemic reaction. The frequency of all adverse events was significantly reduced after the second dose. After the first dose, the anti-SARS-CoV-2 S showed significantly higher titer in the group with swelling, itching, fever, and nausea. Also, the anti-SARS-CoV-2 S titer significantly increased as the grade of fever (p=0.007) and duration of fever (p=0.026) increased; however, there was no significant correlation between immunogenicity and adverse event after the second dose. The group with pain after the first dose showed a greater increase in the anti-SARS-CoV-2 S difference between the second and first doses compared to the group without pain (542.2 U/mL vs. 363.8 U/mL, p=0.037). The frequency of adverse events occurring after the first dose of the ChAdOx1 was significantly reduced after the second dose. Interestingly, the elevation of anti-SARS-CoV-2 S titer was significantly increased in the group with pain after the first dose.

Combining antibody markers for serosurveillance of SARS-CoV-2 to estimate seroprevalence and time-since-infection.

Serosurveillance is an important epidemiologic tool for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), used to estimate infection rates and the degree of population immunity. There is no general agreement on which antibody biomarker(s) should be used, especially with the rollout of vaccines globally. Here, we used random forest models to demonstrate that a single spike or receptor-binding domain (RBD) antibody was adequate for classifying prior infection, while a combination of two antibody biomarkers performed better than any single marker for estimating time-since-infection. Nucleocapsid antibodies performed worse than spike or RBD antibodies for classification, but can be useful for estimating time-since-infection, and in distinguishing infection-induced from vaccine-induced responses. Our analysis has the potential to inform the design of serosurveys for SARS-CoV-2, including decisions regarding a number of antibody biomarkers measured.

SARS-CoV-2 Breakthrough Infection after mRNA-1273 Booster among CoronaVac-Vaccinated Healthcare Workers.

It remains unknown whether the Indonesian healthcare workers (HCWs) who had received two doses of CoronaVac vaccine and one dose of mRNA-1273 booster could be protected during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave. In total, 125 infection-naïve and 10 previously infected HCWs were recruited. The mRNA-1273 booster substantially increased titer of anti-SARS-CoV-2 spike protein receptor-binding domain antibodies. However, the monitoring revealed that 34 out of 125 infection-naïve (27.2%) and 3 out of 10 previously infected HCWs (30.0%) were infected during the Omicron wave. All infected HCWs were either asymptomatic or having mild coronavirus disease 2019 (COVID-19) and subsequently fully recovered, supporting the heterologous prime-boost strategy against COVID-19.

Commercial immunoassays for detection of anti-SARS-CoV-2 spike and RBD antibodies: urgent call for validation against new and highly mutated variants.

Measuring the level of protection conferred by anti-SARS-CoV-2 (trimeric) spike or RBD (receptor binding domain) antibodies (especially total and IgG) is a suitable and reliable approach for predicting biological protection against the risk of infection and severe coronavirus disease 2019 (COVID-19) illness. Nonetheless, SARS-CoV-2 has undergone a broad process of recombination since the identification of the prototype lineage in 2019, introducing a huge number of mutations in its genome and generating a vast array of variants of interest (VoI) and concern (VoC). Many of such variants developed several mutations in spike protein and RBD, with the new Omicron (B.1.1.529) clade displaying over 30 changes, 15 of which concentrated in the RBD. Besides their impact on virus biology, as well as on the risk of detection failure with some molecular techniques (i.e., Sgene dropout), recent evidence suggests that these mutations may also jeopardize the reliability of currently available commercial immunoassays for detecting anti-SARS-CoV-2 antibodies. The antigen (either spike or RBD) and epitopes of the prototype SARS-CoV-2 coated in some immunoassays may no longer reflect the sequence of circulating variants. On the other hand, anti-SARS-CoV-2 antibodies elicited by highly mutated SARS-CoV-2 variants may no longer be efficiently recognized by the currently available commercial immunoassays. Therefore, beside the compelling need to regularly re-evaluate and revalidate all commercially available immunoassays against live virus neutralization assays based on emerging VoCs or VoIs, diagnostic companies may also consider to redevelop their methods, replacing former SARS-CoV-2 antigens and epitopes with those of the new variants.

Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants.

ABSTRACTSerological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22–0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants.IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.

Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma.

The clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, K d, of anti-receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect-based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations.

Anti-SARS-CoV-2 Spike Protein RBD Antibody Levels After Receiving a Second Dose of ChAdOx1 nCov-19 (AZD1222) Vaccine in Healthcare Workers: Lack of Association With Age, Sex, Obesity, and Adverse Reactions.

Response to vaccines generally varies according to individual factors of the vaccinated subjects such as demographics and immune status. While there are various reports of factors associated with immunogenicity of mRNA COVID-19 vaccines, little is known about those of adenovirus vector vaccines. We conducted a prospective observational study to assess the relationships of antibody level with age, sex, body mass index (BMI), and adverse reactions (ARs) to an adenovirus vector vaccine, ChAdOx1 nCoV-19. Healthcare workers who planned to receive both the first and second injections of the ChAdOx1 nCoV-19 vaccine at Hanyang University Hospital, Seoul, Korea, were enrolled in the study. Seven days after each injection, participants were asked to complete an online adverse reaction survey. In addition, anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody concentration was measured 4 weeks after the second injection. All participants (n = 447, 100%) showed serologic positivity (≥ 0.8 U/mL) 4 weeks after the second injection of ChAdOx1 nCoV-19 vaccine. Furthermore, the anti-SARS-CoV-2 S protein RBD concentration was similar among groups when stratified by age, sex, BMI, or presence and severity of AR; multivariable linear regression found no associations between antibody response to the ChAdOx1 nCoV-19 vaccine and age, BMI, sex, and vaccine-induced ARs. In conclusion, age, sex, obesity, and ARs were not associated with antibody responses after two doses of ChAdOx1 nCoV-19 vaccination.

The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice.

The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the receptor-binding domain (RBD) residue change (N501Y), which also emerged independently in other variants of concern such as the beta/B.1.351 and gamma/P.1 strains. Here, we present a functional characterization of the alpha/B.1.1.7 variant and show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.

Safety and immunogenicity of inactivated COVID-19 vaccine in health care workers.

Effective vaccines are essential for controlling the coronavirus disease 2019 (COVID‐19) pandemic. CoronaVac, which is an inactivated virus vaccine, was the first imported COVID‐19 vaccine in Thailand. To investigate the safety and immunogenicity of CoronaVac within the Thai population, we conducted a prospective cohort study among health care workers aged 18–59 years, who received a 2‐dose regimen of CoronaVac 21 days apart between March and April 2021 at the hospital in Samut Sakhon, Thailand. We recruited 185 participants with a mean age of 32 years. Total antibodies against receptor‐binding domain (RBD) and immunoglobulin G (IgG) against nucleocapsid (N) protein of SARS‐CoV‐2 were tested. Total antibodies against RBD were negative before immunization. One volunteer was positive for N, although negative for the RBD antibodies. The seroconversion rate of total antibodies against RBD after the first CoronaVac dose was 67% with a Geometric mean concentration (GMC) of 1.98 U/ml. Following CoronaVac dose 2, the seroconversion rate increased to 100% with a GMC of 92.9 U/ml. The seroconversion rates of IgG against N protein were 1% after dose 1 and 62.8% after dose 2. The overall incidence of adverse reactions was 59.5%. Injection‐site pain was the most common local adverse event (52.4%), while myalgia was the most common systemic adverse event (31.9%). No serious adverse events were observed. A 0–21 days, 2‐dose CoronaVac regimen appears safe, inducing a satisfactory response compared with convalescent serum obtained 4–6 weeks postnatural infection. Antibody responses after 2‐dose CoronaVac were comparable to the convalescent plasma but waned rapidly after 3 months. Therefore, we recommend 2‐dose CoronaVac administration with possible booster doses.

Life Sciences Discovery and Technology Highlights

Life Sciences Discovery and Technology Highlights