Mean Titers Research Articles

Safety and immunogenicity of heterologous ChAdOx1-nCoV19 and BNT162b2 vaccination: A meta-analysis of the heterologous COVID-19 vaccination outcomes.

Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.

Antibody response of Comirnaty vaccine in different immunocompromised groups during the COVID-19 pandemic

Abstract A nationwide vaccination program was initiated on February 23, 2021, in Mongolia by 4 types of vaccines for COVID-19 were offered voluntarily. People at increased risk of severe disease were vaccinated with Comirnaty. In this study, we aimed to compare specific antibody responses after the second dose of the Comirnaty vaccine in different immunocompromised groups. This prospective cohort study was conducted from March–April to July–August of 2021. 225 vaccinees presented an immunocompromised population examined for anti-SARS-CoV-2 RBD-IgG (ELISA, Proteintech, USA) before the first dose of vaccine and RBD-IgG antibodies were measured 14 – 21 days after the second dose of vaccine. An increase of antibody titer more than 3-fold was considered a positive antibody response after vaccination. We could attend to the after the second dose of examination 172 (76.4%) of 225 vaccinees. Antibody response to COVID-19 vaccines was detected in 164 (95.1%) vaccinees that demonstrated positive antibody response. A positive response was found in all (100.0%) immunocompromised (19 patients received anti-cancer chemotherapy, 90 patients received corticosteroids, 63 HIV-infected patients) groups. The mean titer of RBD-IgG antibodies in anti-cancer chemotherapy (185.1±49.1ng/mL, CI95: 161.4–208.8) and corticosteroids group (161.6±70.3 ng/mL, CI95: 147.1–176.2) was significantly higher compared to HIV-infected group (98.8±32.6 ng/mL, CI95: 90.6–107.0). A significant impact on antibody response after the second dose of Comirnaty COVID-19 vaccination was associated with the immunocompromised condition. The study was funded by the Ministry of Health of Mongolia. None

Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents

Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents. To evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents. The NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized. Participants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. Serologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety. Among 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation. The findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents. ClinicalTrials.gov Identifier: NCT04611802.

A multi-center, randomized, controlled, phase-2/3 study to evaluate the safety and immunogenicity of inactivated Japanese encephalitis vaccine in healthy ≥1 to <3 years old Indian children

Background: Japanese encephalitis (JE) is endemic in various parts of India. Due to the limited treatment options available, a new treatment option that is safe and effective is highly expected for the existing medical needs. Methods: In the present randomized Phase-2/3 study, safety, immunogenicity, and reactogenicity of JE-vaccine manufactured by Biological E (BE-JE), given in 2-dose schedule, 28-days apart was assessed in 456 healthy ≥1 to <3-year-old children compared to a licensed JE-vaccine with 3-dose schedule manufactured by Green-cross-corporation (GCC-JE). Results: The BE-JE group demonstrated non‑inferiority compared to GCC-JE group at day-56 as the lower confidence limit of the group difference was not ≥‑10%. At day-56, the geometric mean titre values were significantly higher in BE-JE group compared with the GCC‑JE group (217.97 vs 125.85; p=0.0023). No apparent difference was seen in the safety-profile between both vaccine groups, with all events reported being either mild or moderate in intensity. Also, no significant difference (p=0.2198) was reported in the number of subjects experiencing at least one adverse-event (AE) between both groups. Conclusions: The present study demonstrated BE‑JE’s Vero-cell‑based inactivated JE-vaccine, administered in 2-dose schedule to be immunogenic, well-tolerated, and non-inferior, compared to GCC‑JE-vaccine, administered in a 3‑dose schedule in the pediatric Indian-population. This study was prospectively registered with clinical trial registry of India bearing no CTRI/2011/091/000108 on 14/02/2011.

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1)

BackgroundV114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa–HBV–IPV/Hib and rotavirus RV1 vaccines. MethodsV114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes. Results1184 healthy infants 42–90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 μg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa–HBV–IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa–HBV–IPV/Hib and anti-rotavirus IgA geometric mean titers. ConclusionsAfter a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants.Trial registration: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31

Spotted fever group rickettsiae and Anaplasma phagocytophilum in Borrelia burgdorferi sensu lato seropositive individuals with or without Lyme disease: A retrospective analysis

BackgroundThe Ixodes ricinus tick is the main vector of Borrelia burgdorferi and tick-borne encephalitis virus in Switzerland. Spotted fever group Rickettsiae (SFG) and Anaplasma phagocytophilum have been detected in Swiss ticks, however, information about the extent and clinical presentation of these infections in humans is scant. MethodsIndirect fluorescent antibody tests for SFG rickettsiae and Anaplasma phagocytophilum were performed on serum samples of 121 Borrelia burgdorferi seropositive patients with and without Lyme disease and 43 negative controls. ResultsOut of 121 Borrelia burgdorferi seropositive individuals, 65 (53.7%) were seropositive for IgG and 15 (12.4%) for IgM antibodies to SFG rickettsiae. IgM antibodies were detected more frequently in early-than in late-stage of Lyme disease (12 out of 51 and 2 out of 49; respectively; p ​= ​0.0078). Significantly higher IgG antibody titers against SFG rickettsiae were found in patients with late-stage compared to patients with early-stage Lyme disease (mean titer 1:261 and 1:129, respectively; p ​= ​0.038). This difference was even more pronounced in patients with acrodermatitis chronica atrophicans compared to patients with early stage of Lyme disease (mean titer 1:337 and 1:129, respectively; p ​= ​0.009).In patients presenting with fatigue, headache and myalgia, the prevalence of IgG antibodies against SFG rickettsiae was significantly higher (7 out of 11; 63.6%) than in Borrelia burgdorferi seropositive individuals without clinical illness (1 out of 10; 10%; p ​= ​0.024). IgG antibodies to Anaplasma phagocytophilum were detected in 12 out of 121 individuals (9.9%), no IgM antibodies were found. ConclusionInfections with SFG rickettsiae and Anaplasma phagocytophilum are underdiagnosed and should be ruled out after a tick bite. Further studies are needed to elucidate the possible causative role of SFG rickettsiae for myalgia, headache and long-lasting fatigue after a tick bite and to determine the necessity for an antibiotic treatment.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults

The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n=87). In parallel, cellular immunity (n=45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p<0.0001; Geometric mean titer p=0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ Tlymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

The propositive study: Immunogenicity and safety of a four-component recombinant protein-based vaccine against MenB and a quadrivalent conjugate MenACWY vaccine in people living with HIV.

People living with HIV have been shown to have an increased risk of invasive meningococcal disease. In some countries, meningococcal vaccines are now routinely recommended to all people living with HIV, but no study has yet assessed the immunogenicity and safety of a meningococcal serogroup B vaccine or the co-administration of a MenB and MenACWY vaccine in people living with HIV. This phase IV open-label clinical trial investigated the immunogenicity and safety of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in a population of people living with HIV. Immunogenicity analysis was performed before vaccination and 1 month after the second doses of 4CMenB and MenACWY. Primary outcome measures were serum bactericidal assay geometric mean titres against three MenB reference strains at baseline and 1 month post vaccination, the proportion of participants achieving a putative protective titre of ≥4, and the proportion of participants with a ≥4-fold rise in titre from baseline. Secondary outcome measures were serum bactericidal assay geometric mean titres against MenA, C, W, and Y reference strains at baseline and 1 month post vaccination, the proportion achieving a putative protective titre of ≥8, and the proportion with a ≥4-fold rise in titre from baseline. Safety outcomes were solicited and unsolicited adverse events in the 7 days following vaccination. The trial was registered with clinicaltrials.gov (NCT03682939). In total, 55 participants aged 20-45 years were enrolled. All participants (100%; 95% confidence interval [CI] 93-100) achieved putative protective titres for two of the three MenB strains and for MenA, W, and Y. A total of 98% (95% CI 89-100) achieved a protective titre for the third MenB strain and 94% (95% CI 83-99) for MenC. No serious adverse events were reported. 4CMenB and MenACWY were immunogenic and well-tolerated in a population of people living with HIV 1 month after two doses.

Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice

Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of “ChulaCov19”, a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP). In female BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 μg elicits robust neutralizing antibody (NAb) and T cell responses in a dose-dependent relationship. The geometric mean titers (GMTs) of NAb against wild-type (WT, Wuhan-Hu1) virus are 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induce better cross-NAb against Delta (B.1.617.2) and Omicron (BA.1 and BA.4/5) variants. This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. In a heterologous prime-boost study, ChulaCov19 booster dose generates a 7-fold increase of NAb against Wuhan-Hu1 WT virus and also significantly increases NAb response against Omicron (BA.1 and BA.4/5) when compared to homologous CoronaVac or AZD1222 vaccination. Challenge studies show that ChulaCov19 protects human-ACE-2-expressing female mice from COVID-19 symptoms, prevents viremia and significantly reduces tissue viral load. Moreover, anamnestic NAb response is undetectable in challenge animals. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or boost vaccination and has entered clinical development.

Immunogenicity of High-Dose Egg-Based, Recombinant, and Cell Culture-Based Influenza Vaccines Compared With Standard-Dose Egg-Based Influenza Vaccine Among Health Care Personnel Aged 18-65 Years in 2019-2020.

Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020). In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4. Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes. HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

Five accelerated schedules for the tick-borne encephalitis vaccine FSME-Immun® in last-minute travellers: an open-label, single-centre, randomized controlled pilot trial.

The purpose of this exploratory study was to evaluate different accelerated tick-borne encephalitis (TBE) vaccine schedules for last-minute travellers. In a single-centre, open-label pilot study, 77 TBE-naïve Belgian soldiers were randomized to one of the following five schedules with FSME-Immun®: group 1 ('classical accelerated' schedule) received one intramuscular (IM) dose at Day 0 and Day 14, group 2 two IM doses at Day 0, group 3 two intradermal (ID) doses at Day 0, group 4 two ID doses at Day 0 and Day 7 and group 5 two ID doses at Day 0 and Day 14. The last dose(s) of the primary vaccination scheme were given after 1 year: IM (1 dose) or ID (2 doses). TBE virus neutralizing antibodies were measured in a plaque reduction neutralization test (PRNT90 and 50) at Days 0, 14, 21, 28, Months 3, 6, 12 and 12+21 days. Seropositivity was defined as neutralizing antibody titres ≥10. The median age was 19-19.5 years in each group.Median time to seropositivity up to Day 28 was shortest for PRNT90 in ID-group 4 and for PRNT50 in all ID groups. Seroconversion until Day 28 peaked highest for PRNT90 in ID-group 4 (79%) and for PRNT50 in ID-groups 4 and 5 (both 100%). Seropositivity after the last vaccination after 12 months was high in all groups. Previous yellow fever vaccination was reported in 16% and associated with lower geometric mean titres of TBE-specific antibodies at all-time points.The vaccine was generally well tolerated. However, mild to moderate local reactions occurred in 73-100% of ID compared with 0-38% of IM vaccinations, and persistent discolouration was observed in nine ID vaccinated individuals. The accelerated two-visit ID schedules might offer a better immunological alternative to the recommended classical accelerated IM schedule, but an aluminium-free vaccine would be preferable.

Hepatitis B virus vaccination post serological testing and antibody levels of vaccinated health care workers in Accra, Ghana

IntroductionHepatitis B Virus (HBV) infection is an important occupational hazard to Health Care Workers (HCWs) all over the world. International health organizations have strongly recommended the use of the HBV vaccine, especially among individuals at risk of HBV infection. A laboratory test aimed at measuring Anti-HBs concentration (titer) 1–2 months following a 3-dose vaccination schedule is the most reliable approach for diagnosing seroprotection against HBV. This study sought to assess post-vaccination serological testing, seroprotection against HBV, and associated factors among vaccinated HCWs in Ghana. MethodsA hospital-based analytical cross-sectional study involving 207 HCWs. Pretested questionnaires were used to collect data. 5mls of venous blood were collected from consenting HCWs under strict aseptic conditions and quantitatively analyzed for Anti-HBs using ELISA procedures. SPSS Version 23 was used to analyze data with the level of significance set at 0.05. ResultsMedian age; 33, IQR of 29–39. The post-vaccination serological testing rate was 21.3 %. HCWs with high-risk perception and working at the regional hospital had lower odds of adherence to post-vaccination serological testing (aOR = 0.2; 95 % CI = 0.1–0.7) and (aOR = 0.1; 95 % CI = 0.1–0.6) p < 0.05. The seroprotection rate was 91.3 % (95 % CI = 87 %-95 %). Minority, 18 (8.7 %) of the 207 vaccinated HCWs had antibody titers below 10mIU/mL and were not seroprotected against HBV. Geometric Mean Titers (GMTs) were higher in those who received three doses, took a booster, and were less than 25 kg/m2. ConclusionThe post-vaccination serological testing practice was sub-optimal. The seroprotection rate was higher with higher GMTs in those who adhered to the 3-dose vaccination regimen, took a booster dose, and had BMI < 25 kg/m2. It may be inferred that those with Anti-HBs below 10 IU/ml had their antibodies diminishing or waning off with time or they are true vaccine non-responders. This observation calls for strict adherence to post-vaccination serological testing, especially for HCWs who are at high risk of percutaneous and mucocutaneous exposures that could result in HBV infection.

Immunogenicity Differences of the ChAdOx1 nCoV-19 Vaccine According to Pre-Existing Adenovirus Immunity.

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6-125.0) vs. 51.0 (17.9-122.3), p = 0.024), 2-3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5-926.5) vs. 555.0 (287.3-926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5-655.3) vs. 176.0 (94.3-255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.

Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysis

Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were fromethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06-2.06], P=0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05-2.89], P=0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178-12,852] vs 5888 BAU/ml [5023-6902], P=0.008 and 2851 95% CI [1811-4487] vs 1199 [984-1462], P<0.001 respectively), increments which persisted after adjustment (aGMR 1.26, 95% CI [1.01-1.58], P=0.04 and aGMR 2.01, 95% CI [1.34-3.01], P=0.001). SARS-CoV-2 ELISpot responses to S1 and whole spike peptides (S1+S2 response) were higher in HCWs from South Asian ethnic groups than those from White groups (S1: aIRR 2.33, 95% CI [1.09-4.94], P=0.03; spike: aIRR, 2.04, 95% CI [1.02-4.08]). This study provides evidence that, in an infection naïve cohort, humoral and cellular immune responses to SARS-CoV-2 vaccination are stronger in South Asian HCWs than White HCWs. These differences are most clearly seen in the early period following vaccination. Further research is required to understand the underlying mechanisms, whether differences persist with further exposure to vaccine or virus, and the potential impact on vaccine effectiveness. DIRECT and BELIEVE have received funding from UK Research and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).

Physical Activity: A Strategy to Improve Antibody Response to a SARS-CoV-2 Vaccine Booster Dose in Patients With Autoimmune Rheumatic Diseases.

Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population. This was a phase-4 trial conducted in São Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire. Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P < .01) and had a lower frequency of chronic inflammatory arthritis (P < .01). Adjusted models showed that physically active patients had ∼2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), ∼22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and ∼7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients. Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals.

RESPONSE TO INTRADERMAL ROUTE OF HEPATITIS B VACCINATION IN CHILDREN ON MAINTENANCE HEMODIALYSIS: A SINGLE CENTER EXPERIENCE

Background: To determine the response of intradermal route of hepatitis B vaccine (HBV) in pediatric dialysis patients. Material and Methods: Prospective, observational study carried out in the Hemodialysis Unit, Sindh Institute of Urology and Transplantation (SIUT), Karachi, from October 2021 to September 2022.Patients younger than 18 years, Hepatitis B surface antigen negative irrespective of primary vaccination status, were tested for anti-Hepatitis B antibody titers. Those with levels less than 10IU/L were recruited for intradermal vaccination at 0,1 and 6 months and titers rechecked in the 2nd and 7th month of study. Results: Of the 168 children screened, 81 (48%) patients were eligible for vaccination, however, 52 agreed to participate. Males were 27 (52%). Mean age was 12.18± 2.61 years. End-stage kidney disease due to unknown etiology was the most common cause in 27 (52%) patients with mean dialysis duration being 1.43±1 years. Most, 48 (92%) patients were hypertensive and majority, 47 (90%) patients tested negative for hepatitis C. Final analysis was done on 38 patients. Thirty-four (89.4%) patients responded; 25 (65.8%) being good and excellent responders. Mean antibody titers before intradermal vaccination of 2.87±3 IU/L improved to 383±397 IU/L. Ages 11-15 years showed a statistically significant association with the development of anti-Hepatitis B antibody titers (p value: 0.02) while gender, dialysis duration, pre-vaccination HBs titers, hepatitis C status, hypertension and cause of end-stage kidney disease did not have any effect. Conclusion: ID route of HBV is efficacious in producing seroprotective anti-HBs titers in pediatric ESKD patients. Children 11-15 years had more robust response. Keywords: Children, Hemodialysis, Hepatitis B, Intradermal, Vaccination

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Responses After Community Infections in Children and Adults.

We compared postinfection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (nAb) responses among children and adults while the D614G-like strain and Alpha, Iota, and Delta variants circulated. During August 2020-October 2021, households with adults and children were enrolled and followed in Utah, New York City, and Maryland. Participants collected weekly respiratory swabs that were tested for SARS-CoV-2 and had sera collected during enrollment and follow-up. Sera were tested for SARS-CoV-2 nAb by pseudovirus assay. Postinfection titers were characterized with biexponential decay models. Eighty participants had SARS-CoV-2 infection during the study (47 with D614G-like virus, 17 with B.1.1.7, and 8 each with B.1.617.2 and B.1.526 virus). Homologous nAb geometric mean titers (GMTs) trended higher in adults (GMT = 2320) versus children 0-4 (GMT = 425, P = .33) and 5-17 years (GMT = 396, P = .31) at 1-5 weeks postinfection but were similar from 6 weeks. Timing of peak titers was similar by age. Results were consistent when participants with self-reported infection before enrollment were included (n = 178). The SARS-CoV-2 nAb titers differed in children compared to adults early after infection but were similar by 6 weeks postinfection. If postvaccination nAb kinetics have similar trends, vaccine immunobridging studies may need to compare nAb responses in adults and children 6 weeks or more after vaccination.

A longitudinal study of hepatitis B surface antibody level after the accelerated vaccination protocol applied to health workers in a hospital of Thailand

BackgroundHepatitis B infection persists in Thailand, especially among health personnel. The current immunization protocol (3 doses in 6 months) is too slow to protect against infection; thus, an accelerated protocol has been in place as the accelerated protocol at a supra-tertiary hospital since 2014. AimTo measure the anti-HBs level 1, 2, and 5 years post-accelerated vaccination of health personnel who had received the hepatitis vaccine using. MethodsA descriptive study was conducted. Electrochemiluminescence Immunoassay; ECLIA (Roche Diagnostic Cobas 6000, Indianapolis, IN) was used to measure the anti-HB level 1, 2, and 5 years after the third dose in 73, 58, and 20 participants, respectively. FindingsThe starting group number declined over time as workers resigned or transferred away, so the tested number in years 2 and 5 represents the remaining workers that started the study in year 1. The respective geometric mean titer after 1, 2, and 5 years was 1765.8, 164.7, and 107.9 mIU/mL. Fifty-four participants (93.1%) had lower antibody levels in the second year than in the first year. Nine participants (45.0%) had lower antibody levels in the fifth year than in the second year. ConclusionThe anti-HBs level declined from the first to the second and fifth years; however, the anti-HBs level persisted at a protective level. The accelerated protocol benefited health personnel, protecting them from hepatitis B infection.