Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

BackgroundAlthough several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays.MethodsThis prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20–64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays.ResultsAmong the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively.ConclusionsTwo BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.     

Humoral immune response characterization of heterologous prime-boost vaccination with CoronaVac and BNT162b2

BackgroundVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven to be a successful strategy for prevent severe infections. CoronaVac and BNT162b2 are the most used vaccines worldwide, but their use in heterologous vaccination schedules is still subjected to evaluation.MethodsFifty healthy individuals who received heterologous prime-boost vaccination with CoronaVac and BNT162b2 were enrolled in a post-vaccination serological follow-up longitudinal prospective study. We evaluated specific serum anti-receptor binding domain (RBD) IgG antibody levels, and their capacity to block RBD-ACE2 interaction with a surrogate neutralization assay. In 20 participants, we assessed antibody binding kinetics by surface plasmon resonance, and Fc-mediated functions by ADCC and ADCP reporter assays.ResultsOur baseline seronegative cohort, displayed seroconversion after two doses of CoronaVac and an important decrease in serum anti-RBD IgG antibodies levels 80 days post-second dose. These levels increased significantly early after the third dose with BNT162b2, but 73 days after the booster we found a new fall. Immunoglobulin functionalities showed a similar behavior.ConclusionsThe heterologous prime-boost vaccination with CoronaVac and BNT162b2 generated an impressive increase in serum anti-RBD specific antibody levels followed by a drop. Nevertheless, these titers remained well above those found in individuals only vaccinated with CoronaVac in the same elapsed time. Serum IgG levels showed high correlation with antibody binding analysis, their capacity to block RBD-ACE2 interaction, and Fc-effectors mechanisms. Our work sheds light on the humoral immune response to heterologous vaccination with CoronaVac and BNT162b2, to define a post-vaccination correlate of protection against SARS-CoV-2 infection and to discuss the scheduling of future vaccine boosters in general population.     

Comparison of the effectiveness and duration of anti-RBD SARS-CoV-2 IgG antibody response between different types of vaccines: Implications for vaccine strategies

Background and objectivesLittle is known about the efficacy and durability of anti-RBD IgG antibodies induced by certain SARS-CoV-2 vaccines. It has been shown that neutralizing antibodies are associated with the protection against re-infection. This study aims to compare the mean titers, duration, and efficacy of generating protective anti-RBD IgG antibody response among recipients of Pfizer/BioNTech, AstraZeneca, Sputnik V, Johnson & Johnson, Moderna, and Sinopharm COVID-19 vaccines. In addition, we aimed to compare the susceptibility of getting COVID-19 breakthrough infections after various types of vaccines.Materials and methodsSamples from 2065 blood bank donors and healthcare workers at King Hussein Cancer Center (KHCC) were collected between February and September 2021. Anti-Spike/RBD IgG levels were measured using Chemiluminescent microparticle-immunoassay (CMIA) (ARCHITECT IgG II Quant test, Abbott, USA).ResultsThe mean titer of anti-RBD IgG levels was significantly diverse among different types of vaccines. The highest titer level was seen in participants who took a third booster vaccine shot, followed by Pfizer/BioNTech, AstraZeneca, and Sinopharm vaccine. The mean titer levels of anti-RBD IgG antibodies in the Pfizer vaccinated group was the highest after vaccination but started to drop after 60 days from vaccination unlike AstraZeneca and Sinopharm vaccine-induced antibodies where the mean titers continued to be stable until 120 days but their levels were significantly lower. Most of the breakthrough infections were among the Sinopharm vaccinated group and these breakthroughs happened at random times for the three main types of vaccines.ConclusionsOur data demonstrate that the mean-titer of anti-RBD IgG levels drop after four months which is the best time to take the additional booster shot from a more potent vaccine type such as mRNA vaccines that might be needed in Jordan and worldwide.     

Immunogenicity,efficacy, and safety of CoronaVac and Pfizer/BioNTech mRNA vaccines in patients with psoriasis receiving systemic therapies: A prospective cohort study

Background and objectivesEvidence of immune response to COVID-19 vaccine in psoriasis patients on biological agents is lacking. This study aimed to evaluate SARS-CoV-2 antibody levels following vaccination with CoronaVac or Pfizer/BioNTech mRNA in patients using biological agents or methotrexate, high-titer antibody levels achievement rate, and impact of medications on immunogenicity.MethodsThis noninterventional, prospective cohort study included 89 patients and 40 controls vaccinated with two doses of inactivated (CoronaVac) or Pfizer/BioNTech mRNA vaccines. Anti-spike and neutralising antibodies were analysed before and three to six weeks after the second dose. Adverse effects and symptomatic COVID-19 were assessed.ResultsMedian anti-spike and neutralising antibody titers after CoronaVac were significantly lower in patients than controls (57.92 U/mL vs 125.4 U/mL, and 1/6 vs 1/32, respectively, p < 0.05). Patients were less likely to achieve high-titer anti-spike antibody levels (25.6 % vs 50 %). Infliximab was associated with attenuated vaccine response.Pfizer/BioNTech vaccine induced comparable median anti-spike (2,080 U/mL vs 2,976.5 U/mL,) and neutralising antibody levels (1/96 vs 1/160) in patients and controls, respectively (p > 0.05). High-titer anti-spike and neutralising antibodies development rates were comparable among patients and controls (95.2 % vs 100 %, and 30.4 % vs 50.0 %, respectively, p > 0.05).Nine (10.1 %) COVID-19 cases- all mild - were identified. Psoriasis flare was seen in 6.74 %, mostly after Pfizer/BioNTech vaccine.ConclusionPsoriasis patients treated with biological agents and methotrexate developed similar response to mRNA vaccine but weaker response to inactivated vaccine. Infliximab reduced response to the inactivated vaccine. Adverse effects were more frequent with mRNA vaccine, but none was severe.     

Immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 with 12-dose vials: An interim analysis

BackgroundChAdOx1 nCoV-19 (AZD 1222) is the main vaccine planned for general administration in Thailand. This vaccine is stored in multiple-dose vials meant to be administered to 10 recipients with a volume of 0.5 mL for each dose. However, the vaccine vials were overfilled, which allows the administration of more than 10 doses per vial. We have stipulated the preparation and use of ChAdOx1 nCoV-19 vaccine using traditional 21 or 25G needles and planned to investigate the immune responses of participants who were administered the ChAdOx1 nCoV-19 vaccine using this technique.MethodsWe measured anti-SARS-CoV-2 anti-spike RBD IgG and neutralising antibody using a surrogate virus neutralising test (sVNT) among adults aged 18–72 years on average of 8.57 weeks (IQR 6.85–8.93) after the first dose of ChAdOx1 nCoV-19 vaccine. The primary outcome was the antibody level. The secondary outcomes included adverse events, factors affecting antibody levels, and incidence of COVID-19 infection.FindingsIn all, 60 participants comprised 25 males and 35 females. The mean age was 53.70 ± 17.48 years. BMI was 23.45 ± 3.69 kg/m². Tests for the neutralising antibody were positive in 60% of the participants (71.4% among males and 44% among females). The median anti-SARS-CoV-2 QuantiVac (anti-spike IgG) level among male and female samples was 111.83 BAU/mL (IQR 73.48–196.74 BAU/mL) and 159.65 BAU/mL (IQR 100.39–371.81), respectively. The positive QuantiVac value of male and female samples was 88.00% and 98.44%, respectively (p-value = 0.382) .A good correlation was observed between neutralising Ab and anti-spike RBD IgG.ConclusionPatients receiving 12-dose per vial injections of ChAdOx1 nCoV-19 exhibited high levels of immunity without severe side effects. This technique can be adopted to maximise the number of doses per vial while preserving vaccine effectiveness.     

Previous SARS-CoV-2 Infection,Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents

ObjectivesOlder nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group.DesignLongitudinal cohort study.Setting and ParticipantsResidents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine.MethodsComprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity.ResultsOf 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32–3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89–4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: ?0.05; 95% CI: ?0.08 to ?0.02; P < .001) and frailty (β: ?0.22; 95% CI: ?0.33 to ?0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity.Conclusions and ImplicationsIn older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.     

Dynamic of anti-spike receptor binding domain (RBD) levels and short-term adverse events following a heterologous booster dose of BNT162b2 after two doses of CoronaVac in Thai health care workers

BackgroundCoronaVac was administered as the primary COVID-19 vaccine for Thai health care workers (HCWs) in early 2021 in response to the epidemic of new variants. This study aimed to evaluate the dynamic of humoral immune response as well as the short-term side effects resulting from the booster dose of BNT162b2 following completion of a CoronaVac double-dose in Thai HCWs.MethodsThis study was conducted at a teaching hospital in Northern Thailand during August and September 2021. The participants were 50 HCWs who were vaccinated with 2 doses of CoronaVac and were scheduled to receive a booster dose of BNT162b2. Anti-SARS-CoV-2 IgG antibodies levels and short-term side effects were assessed. The anti-RBD level was determined using Architect SARS-CoV-2 IgG II Quant (Abbott).ResultOf the 50 participants, 37 were female. The median age was 33.0 years old. The average time between the second CoronaVac shot and the BNT162b2 booster shot was 81.7 days (SD = 25.0). The median anti-SARS-CoV-2 IgG antibody level on booster vaccination date, as well as day 14, and day 28 after the booster were 335.5 AU/ml, 31,613.5 AU/ml, and 20,311.9 AU/ml, respectively. Fourteen days after the booster, 94% of participants had anti-SARS-CoV-2 IgG antibody levels higher than 50.0 AU/ml. Being female, higher log anti-SARS-CoV-2 IgG antibodies prior to booster vaccination, and longer interval between the second shot and the booster shot were found to be significantly associated with higher levels of anti-SARS-CoV-2 IgG antibodies at both day 14 and day 28 after the booster. There were no reports of serious adverse events.ConclusionA booster dose of BNT162B2 promoted a high level of anti-SARS-CoV-2 IgG antibodies among HCWs who received 2 doses of CoronaVac. The time between the second CoronaVac shot and the booster shot should be at least three months. There were no severe adverse effects observed.     

Dynamics of antibody titers and cellular immunity among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA vaccine

BackgroundThe antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection.MethodsThis prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination.ResultsA total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic.ConclusionsBoth humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent.UMIN Clinical Trials Registry IDUMIN000043340.     

Robust immunogenicity of a third BNT162b2 vaccination against SARS-CoV-2 Omicron variant in a naïve New Zealand cohort

The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted. This adult cohort of 298 participants, oversampled for at-risk populations, was composed of 29% Māori and 28% Pacific peoples, with 40% of the population aged 55+. A significant proportion of the cohort was obese and presented with at least one comorbidity. Sera were collected 28 days and 6 months post second vaccination and 28 days post third vaccination. SARS-CoV-2 anti-S IgG titres and neutralising capacity using surrogate viral neutralisation assays against variants of concern, including Omicron BA.1, were investigated. The incidence of SARS-CoV-2 infection, within our cohort, prior to third vaccination was very low (<6%). This study found a third vaccine significantly increased the mean SARS-CoV-2 anti-S IgG titres, for every demographic subgroup, by a minimum of 1.5-fold compared to titres after two doses. Diabetic participants experienced a greater increase (∼4-fold) in antibody titres after their third vaccination, compared to non-diabetics (increase of ∼ 2-fold). This corrected for the deficiency in antibody titres within diabetic participants which was observed following two doses. A third dose also induced a neutralising response against Omicron variant BA.1, which was absent after two doses. This neutralising response improved regardless of age, BMI, ethnicity, or diabetes status. Participants aged ≥75 years consistently had the lowest SARS-CoV-2 anti-S IgG titres at each timepoint, however experienced the greatest improvement after three doses compared to younger participants. This study shows that in the absence of prior SARS-CoV-2 infection, a third Pfizer-BioNTech BNT162b2 vaccine enhances immunogenicity, including against Omicron BA.1, in a cohort representative of at-risk groups in the adult New Zealand population.     

BBIBP-CorV vaccination accelerates anti-viral antibody responses in heterologous Omicron infection: A retrospective observation study in Shanghai

ObjectivesTo investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection.Methods440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed.ResultsBBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients.ConclusionsBBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.     

Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine (Sinopharm BBIBP-CorV) coadministered with quadrivalent split-virion inactivated influenza vaccine and 23-valent pneumococcal polysaccharide vaccine in China: A multicentre,non-inferiority,open-label,randomised, controlled,phase 4 trial

BackgroundThe safety and immunogenicity of the coadministration of an inactivated SARS-CoV-2 vaccine (Sinopharm BBIBP-CorV), quadrivalent split-virion inactivated influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults in China is unknown.MethodsIn this open-label, non-inferiority, randomised controlled trial, participants aged ≥ 18 years were recruited from the community. Individuals were eligible if they had no history of SARS-CoV-2 vaccine or any pneumonia vaccine and had not received an influenza vaccine during the 2020–21 influenza season. Eligible participants were randomly assigned (1:1:1), using block randomization stratified, to either: SARS-CoV-2 vaccine and IIV4 followed by SARS-CoV-2 vaccine and PPV23 (SARS-CoV-2 + IIV4/PPV23 group); two doses of SARS-CoV-2 vaccine (SARS-CoV-2 vaccine group); or IIV4 followed by PPV23 (IIV4/PPV23 group). Vaccines were administered 28 days apart, with blood samples taken on day 0 and day 28 before vaccination, and on day 56.ResultsBetween March 10 and March 15, 2021, 1152 participants were recruited and randomly assigned to three groups (384 per group). 1132 participants were included in the per-protocol population (375 in the SARS-CoV-2 + IIV4/PPV23 group, 380 in the SARS-CoV-2 vaccine group, and 377 in the IIV4/PPV23 group). The seroconversion rate (100 % vs 100 %) and GMT (159.13 vs 173.20; GMT ratio of 0.92 [95 % CI 0.83 to 1.02]) of SARS-CoV-2 neutralising antibodies in the SARS-CoV-2 + IIV4/PPV23 group was not inferior to those in the SARS-CoV-2 vaccine group. The SARS-CoV-2 + IIV4/PPV23 group was not inferior to the IIV4/PPV23 group in terms of seroconversion rates and GMT of influenza virus antibodies for all strains except for the seroconversion rate for the B/Yamagata strain. The SARS-CoV-2 + IIV4/PPV23 group was not inferior to the IIV4/PPV23 group regarding seroconversion rates and GMC of Streptococcus pneumoniae IgG antibodies specific to all serotypes. All vaccines were well tolerated.ConclusionsThe coadministration of the inactivated SARS-CoV-2 vaccine and IIV4/PPV23 is safe with satisfactory immunogenicity.This study is registered with ClinicalTrials.gov, NCT04790851.     

Evaluation of the effect of maternally derived antibody on response to MMR vaccine in Thai infants

BackgroundAlthough the number of measles cases declined globally in response to anti-measles immunisation campaigns, measles has re-emerged. A review of current vaccination policies is required to improve measles elimination strategies.MethodsA pseudotype-based virus neutralisation assay (PVNA) was used to measure neutralising antibody titres in serum samples collected from Thai infants at six timepoints before and after two-doses of MMR (1&2) vaccination (ClinicalTrials.gov no. NCT02408926). Vesicular stomatitis virus (VSV) luciferase pseudotypes bearing the haemaglutinin (H) and fusion (F) glycoproteins of measles virus (MeV) were prepared. Serial dilutions of serum samples were incubated with VSV (MeV) pseudotypes and plated onto HEK293-human SLAM1 cells; the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity.ResultsNeutralising antibody titres in infants born with high levels of maternal immunity (H group) persisted at the time of the first MMR vaccination, and those infants did not respond effectively by developing protective titres. In contrast, infants with lower maternal immunity (L group) developed protective titres of antibody following vaccination. Responses to the second MMR vaccination were significantly higher (P = 0.0171, Wilcoxon signed-rank test) in the H group. The observed correlation between anti-MeV IgG level and neutralising antibody titre in Thai infants indicates the possibility of using rapid IgG testing as a surrogate measure for neutralising activity to define clinical protection levels within populations.ConclusionThese results demonstrate that varying the timing of the first MMR immunisation according to the level of acquired maternal immunity could increase vaccination immunogenicity and hence accelerate measles eradication.     

Safety and efficacy of COVID-19 prime-boost vaccinations: Homologous BBIBP-CorV versus heterologous BNT162b2 boosters in BBIBP-CorV-primed individuals

BackgroundBooster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied.MethodsWe conducted a non-randomized, non-blinded phase II observational community trial across Bahrain, investigating the reactogenic and immunogenic response of participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological status was determined at baseline and on the following 8th week. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling.Results305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study, with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred.ConclusionHeterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated.Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.     

Delay between COVID-19 complete vaccination and SARS-CoV-2 infection among healthcare workers

ObjectivesHealthcare workers (HCWs), at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccination, which became mandatory for them on September 15th, 2021 in France. In November they were confronted to the fifth COVID-19 wave despite excellent vaccine coverage. We aimed to estimate the incidence of SARS-CoV-2 infection after complete vaccination among HCWs with different vaccination schemes, and its determinants.MethodsWe enrolled all HCWs in the university hospital of Rennes, France who had received complete vaccination (two doses of COVID-19 vaccine). The delay from last vaccination dose to SARS-CoV-2 infection was computed. Fitted mixed Cox survival model with a random effect applied to exposure risk periods to account for epidemic variation was used to estimate the determinants of SARS-CoV-2 infection after complete vaccination.ResultsOf the 6674 (82%) HCWs who received complete vaccination (36% BNT162b2, 29% mRNA-1273, and 34% mixed with ChAdOx1 nCoV-19) and were prospectively followed-up for a median of 7.0 [6.3–8.0] months, 160 (2.4%) tested positive for SARS-CoV-2 by RT-PCR. Incidence density of SARS-CoV-2 infection after complete vaccination was 3.39 [2.89–3.96] infections per 1000 person-month. Median time from vaccine completion to SARS-CoV-2 infection was 5.5 [3.2–6.6] months. Using fitted mixed Cox regression with the delay as a time-dependent variable and random effect applied to exposure risk periods, age (P < 0.001) was independently associated with the incidence of SARS-CoV-2 infection. Vaccine schemes were not associated with SARS-CoV-2 infection (P = 0.068). A period effect was significantly associated with the incidence of SARS-CoV-2 infection (P < 0.001).ConclusionsIn this real-world study, incidence of SARS-CoV-2 infection increases with time in fully vaccinated HCWs with no differences according to the vaccination scheme. The short delay between complete vaccination and incident SARS-CoV-2 infection highlights the need for sustained barrier measures even in fully vaccinated HCWs.     

Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

BackgroundWith COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination.MethodsMultiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech).ResultsThe sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80–90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50–81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants.ConclusionsSerological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.     

One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine

BackgroundA third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination.MethodsA prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4–6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded.ResultsSeventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months.ConclusionsA third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.     

Predictors of serological non-response to the 13-valent pneumococcal conjugate vaccine followed by the 23-valent polysaccharide vaccine among adults living with HIV

BackgroundPeople living with HIV (PLWH) have higher incidence of pneumococcal disease compared to people without HIV. Immunization with pneumococcal vaccines is recommended, but serological non-response to pneumococcal vaccination is common for largely unknown reasons.MethodsPLWH on antiretroviral treatment and no prior pneumococcal vaccination received the 13-valent pneumococcal conjugate vaccine (PCV13) followed 60 days later by the 23-valent polysaccharide vaccine (PPV23). Serological response was evaluated 30 days post-PPV23 by antibodies against 12 serotypes covered by both PCV13 and PPV23. Seroprotection was defined as a ≥2-fold rise to a level above 1.3 µg/ml in geometric mean concentration (GMC) across all serotypes. Associations with non-responsiveness were evaluated by logistic regression.ResultsFifty-two virologically suppressed PLWH (median age of 50 years (IQR 44–55) and median CD4 count of 634 cells/mm³ (IQR 507–792)) were included. Forty-six percent (95 % CI 32–61, n = 24) achieved seroprotection. Serotypes 14, 18C and 19F had the highest, and serotypes 3, 4 and 6B the lowest GMCs. Pre-vaccination GMC levels less than 100 ng/ml were associated with increased odds of non-responsiveness compared to levels above 100 ng/ml (adjusted OR 8.7, 95 % CI 1.2–63.6, p = 0.0438).ConclusionLess than half of our study population achieved anti-pneumococcal seroprotective levels following PCV13 and PPV23 immunization. Low pre-vaccination GMC levels were associated with non-response. Further research is required to optimize vaccination strategies that achieve higher seroprotection in this high-risk group.     

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease

BackgroundImmunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity.AimsThis study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine.MethodsWe conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose.ResultsOur study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups.ConclusionsAnti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.     

Immunogenicity of adjuvanted plant-produced SARS-CoV-2 Beta spike VLP vaccine in New Zealand white rabbits

The outbreak of the SARS-CoV-2 global pandemic heightened the pace of vaccine development with various vaccines being approved for human use in a span of 24 months. The SARS-CoV-2 trimeric spike (S) surface glycoprotein, which mediates viral entry by binding to ACE2, is a key target for vaccines and therapeutic antibodies. Plant biopharming is recognized for its scalability, speed, versatility, and low production costs and is an increasingly promising molecular pharming vaccine platform for human health. We developed Nicotiana benthamiana-produced SARS-CoV-2 virus-like particle (VLP) vaccine candidates displaying the S-protein of the Beta (B.1.351) variant of concern (VOC), which triggered cross-reactive neutralising antibodies against Delta (B.1.617.2) and Omicron (B.1.1.529) VOCs. In this study, immunogenicity of the VLPs (5 µg per dose) adjuvanted with three independent adjuvants i.e. oil-in-water based adjuvants SEPIVAC SWE^TM (Seppic, France) and “AS IS” (Afrigen, South Africa) as well as a slow-release synthetic oligodeoxynucleotide (ODN) adjuvant designated NADA (Disease Control Africa, South Africa) were evaluated in New Zealand white rabbits and resulted in robust neutralising antibody responses after booster vaccination, ranging from 1:5341 to as high as 1:18204. Serum neutralising antibodies elicited by the Beta variant VLP vaccine also showed cross-neutralisation against the Delta and Omicron variants with neutralising titres ranging from 1:1702 and 1:971, respectively. Collectively, these data provide support for the development of a plant-produced VLP based candidate vaccine against SARS-CoV-2 based on circulating variants of concern.