Final Vaccine Dose Research Articles

Evaluation of ichroma™ COVID-19 interferon gamma release assay for detection of vaccine-induced immunity in healthcare workers

We compared the performance of a new interferon gamma release assay (IGRA) format assay, the ichroma™ COVID-19 IGRA (IGRA-SARS), with that of thewidely used QuantiFERON SARS-CoV-2 ELISA kit (QFN-SARS) in vaccinated healthcare workers (HCWs). Additionally, we analyzed the long-term changes in IGRA results after the final vaccine dose. A total of 383 specimens from 281 HCWs were enrolled in this study, and the results of SARS-IGRA andQFN-SARS assays were compared. In addition, we performed the receive operator curve analysis to estimate the optimal cut-off value for IGRA-SARS. For all specimens, IGRA-SARS and QFN-SARS showed 75.7% and 64.2% of the positive results, respectively. The absolute agreement between IGRA-SARS and QFN-SARS was 80.0%, and the Fleiss' κ value was 0.525, indicating moderate agreement. ROC curve analysis of the IGRA-SARS results showed a cut-off value of >0.254IU/mL, which was consistent with the manufacturer's specifications. The positive rates of both IGRA assays decreased significantly after a postvaccination period of 6months. IGRA-SARS showed acceptable performance in the detection of vaccine-induced immunity against COVID-19; however, harmonization of IGRA assays has notyet been achieved. Additionally, the significant decline of positive rates of IGRA after the last vaccination wouldsupport the necessity of booster vaccination after a postvaccination period of 6months.

Measuring the Effectiveness of COVID-19 Vaccines Used during a Surge of the Delta Variant of SARS-CoV-2 in Bangladesh: A Test-Negative Design Evaluation.

From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries.

GMZ2 Vaccine-Induced Antibody Responses, Naturally Acquired Immunity and the Incidence of Malaria in Burkinabe Children.

GMZ2 is a malaria vaccine candidate evaluated in a phase 2b multi-centre trial. Here we assessed antibody responses and the association of naturally acquired immunity with incidence of malaria in one of the trial sites, Banfora in Burkina Faso. The analysis included 453 (GMZ2 = 230, rabies = 223) children aged 12-60 months old. Children were followed-up for clinical malaria episodes for 12 months after final vaccine administration. Antibody levels against GMZ2 and eleven non-GMZ2 antigens were measured on days 0 and 84 (one month after final vaccine dose). Vaccine efficacy (VE) differed by age group (interaction, (12-35 months compared to 36-60 months), p = 0.0615). During the twelve months of follow-up, VE was 1% (95% confidence interval [CI] -17%, 17%) and 23% ([CI] 3%, 40%) in the 12 - 35 and 36 – 60 months old children, respectively. In the GMZ2 group, day 84 anti-GMZ2 IgG levels were associated with reduced incidence of febrile malaria during the follow up periods of 1-6 months (hazard ratio (HR) = 0.87, 95%CI = (0.77, 0.98)) and 7-12 months (HR = 0.84, 95%CI = (0.71, 0.98)) in the 36-60 months old but not in 12-35 months old children. Multivariate analysis involving day 84 IgG levels to eleven non-vaccine antigens, identified MSP3-K1 and GLURP-R2 to be associated with reduced incidence of malaria during the 12 months of follow up. The inclusion of these antigens might improve GMZ2 vaccine efficacy.

Achieving safe surgery after COVID-19 vaccination.

Achieving safe surgery after COVID-19 vaccination.

Differential antibody response to COVID-19 vaccines across immunomodulatory therapies for multiple sclerosis

BackgroundPrior studies suggest reduced humoral response to COVID-19 vaccination in immunosuppressed populations. Disease modifying therapies (DMTs) for multiple sclerosis (MS) have variable immunomodulatory effects, and limited data are available for all DMTs. We aimed to determine the impact of DMTs on antibody response to COVID-19 vaccination among MS patients. MethodsPatients with documented COVID-19 vaccination dates and anti-spike antibody results post-vaccination were identified between March-August 2021. Clinical data were retrospectively abstracted from chart review. Deidentified data were analyzed to evaluate antibody response, and multivariable logistic regression analyses were used to identify clinical and demographic predictors of antibody response. Data analysis was completed with SAS Studio, v3.8. ResultsA total of 353 individuals had documented COVID-19 vaccine and antibody test dates (58% Pfizer, 38% Moderna, and 4% Johnson & Johnson). Of these 353 patients, 72% developed antibodies, with a mean antibody test interval of 53 days (median 46) post final vaccine dose. 100% of those on no DMT (n = 34), injectables (n = 20), teriflunomide (n = 10), natalizumab (n = 71), and 97.8% of those on fumarates (n = 46/47) had a positive antibody result. One patient on cladribine (n = 1) had a negative antibody result. Of those on sphingosine-1 phosphate (S1P) modulators, 72.4% (n = 21/29) had a positive antibody result. Of those on anti-CD20 therapies, 37.6% (n = 53/141) had a positive antibody result. Multivariate modeling of the total cohort showed anti-CD20 therapy was significantly associated with lower odds of positive antibody response (OR = 0.024, 95% CI 0.01;0.05, p < 0.0001). Among S1P modulators, increased duration of therapy, and not lymphopenia, may be associated with lower odds of positive antibody response. Multivariate modeling of anti-CD20 therapies showed therapy duration < 1 year (OR 8.14, 95% CI 2.896;22.898 p < .0001) and prior COVID-19 infection (OR = 3.95, 95% CI 1.137;13.726, p = .03) were significantly associated with higher odds of a positive antibody response. In patients with recent B-cell data, mean B-cell count was higher in antibody-positive individuals compared to antibody-negative (32.9 vs. 3.9 cells, p = .0056). ConclusionMS DMTs had variable impact on antibody response with mRNA and viral vector COVID-19 vaccines. All patients on no DMT, interferons, glatiramer acetate, teriflunomide, natalizumab, and nearly all on fumarates had positive antibody responses post-vaccine. S1P modulators and anti-CD20 therapies attenuated antibody response post-vaccine. For patients on anti-CD20 therapies, shorter duration of therapy and prior COVID-19 infection predicted positive antibody response. Further studies are needed to determine clinical significance of antibody testing, development of cellular mediated immunity, and benefits of booster vaccinations.

Neutralization assays for SARS-CoV-2: Implications for assessment of protective efficacy of COVID-19 vaccines.

The WHO emergency use-listed (EUL) COVID-19 vaccines were developed against early strains of SARS-CoV-2. With the emergence of SARS-CoV-2 variants of concern (VOCs) - Alpha, Beta, Gamma, Delta and Omicron, it is necessary to assess the neutralizing activity of these vaccines against the VOCs. PubMed and preprint platforms were searched for literature on neutralizing activity of serum from WHO EUL vaccine recipients, against the VOCs, using appropriate search terms till November 30, 2021. Our search yielded 91 studies meeting the inclusion criteria. The analysis revealed a drop of 0-8.9-fold against Alpha variant, 0.3-42.4-fold against Beta variant, 0-13.8-fold against Gamma variant and 1.35-20-fold against Delta variant in neutralization titres of serum from the WHO EUL COVID-19 vaccine recipients, as compared to early SARS-CoV-2 isolates. The wide range of variability was due to differences in the choice of virus strains selected for neutralization assays (pseudovirus or live virus), timing of serum sample collection after the final dose of vaccine (day 0 to 8 months) and sample size (ranging from 5 to 470 vaccinees). The reasons for this variation have been discussed and the possible way forward to have uniformity across neutralization assays in different laboratories have been described, which will generate reliable data. Though in vitro neutralization studies are a valuable tool to estimate the performance of vaccines against the backdrop of emerging variants, the results must be interpreted with caution and corroborated with field-effectiveness studies.

98. COVID-19 Vaccine Breakthrough Hospitalizations and Deaths in the Veterans Health Administration

BackgroundA COVID-19 vaccine breakthrough infection is defined as SARS-CoV-2 RNA or antigen detected ≥ 14 days after completion of a final vaccine dose. CDC’s May 25 MMWR report of 10,262 vaccine breakthrough infections in the U.S. is likely an underestimate. Herein, we report Veterans Health Administration (VHA) breakthrough cases, focusing on hospitalizations and deaths.MethodsWe extracted COVID-19 vaccine breakthrough infections tested between 1/19/2021 and 4/30/2021 from the VHA Corporate Data Warehouse (including screening tests). We reviewed medical records of cases who died and/or were hospitalized within 14 days of SARS-CoV-2 positive test for clinician documentation of conditions deemed high risk for COVID-19 and to confirm hospitalization or death was related to COVID-19. SARS-CoV-2 whole genome sequencing (Clear Labs platform) and antigen testing (Abbott BinaxNOW) from available patient samples were performed and Pangolin lineage determined.Results1,142 COVID-19 vaccine breakthrough infections were identified. 357/1,142 (31.3%) were hospitalized and/or died. 1,085 (95%) were male (Table 1), and median age was 72.5 years (74 years for hospitalized/deceased patients). COVID-19 infection contributed to hospitalization and/or death in 139 (38.9%) cases. The remaining 218 (61.1%) were hospitalized or died of causes apparently unrelated to COVID-19. Smoking and heart conditions were seen most frequently among hospitalized/deceased breakthrough cases (Table 2). Variant B.1.1.7 was predominant, present in 17/27 (63%) total samples sequenced, and 13/21 (61.9%) hospitalized/deceased. (Table 3). Of 21 sequenced hospitalized/deceased cases, SARS-CoV-2 antigen positivity was present in 11 (52.4%). ConclusionCompared to CDC reported breakthrough infections, VHA cases were more male, older, and hospitalized/died at higher frequency. Further study is needed to determine the contribution of specific underlying conditions, COVID-19 vaccine formulations and variants on hospitalization and death among COVID-19 vaccine breakthrough infections. Sequencing efforts for breakthrough cases should be intensified, particularly for those presenting with more severe infections.Disclosures All Authors: No reported disclosures

Oral Ixazomib in Untreated Follicular Lymphoma Permits COVID-19 Vaccine Response and Its Efficacy Is Associated with Clinical Factors and Gene Expression Signatures

Oral Ixazomib in Untreated Follicular Lymphoma Permits COVID-19 Vaccine Response and Its Efficacy Is Associated with Clinical Factors and Gene Expression Signatures

The optimal interval for post-vaccination serological test in infants born to mothers with positive hepatitis B surface antigen

ABSTRACT Postvaccination serologic testing (PVST) is utilized to monitor the success or failure of vaccination against hepatitis B virus (HBV) infection in infants of hepatitis B surface antigen (HBsAg) positive mothers. This secondary analysis of 1255 infants of HBsAg-positive mothers at 7–14 months age included in two prospective studies aimed to determine the optimal interval for PVST after three hepatitis B vaccine doses. HBsAg and anti-HBs were quantitatively tested with microparticle enzyme immunoassay. The average PVST interval was 3.8 ± 2.2 months. Overall, 1.7% (21/1255) infants had anti-HBs <10 mIU/mL. The non-response rates were 1.6%, 1.1%, 0.9%, 0.7%, 1.1%, 0.7%, and 5.7% when PVST was performed at an interval of 1, 2, 3, 4, 5, 6, and 7–8 months after the third vaccine dose, respectively. Compared with 1 month of PVST interval, the non-response rate in infants who underwent PVST 7–8 months was significantly higher (χ2 = 4.616, P = .032). Anti-HBs titers were significantly declined in infants with medium responses when PVST was performed with longer intervals (χ2 = 27.592, P < .001), actually declined from interval of 6, and 7–8 months (Z = −3.177, P = .001 and Z = −3.715, P < .001), respectively. These results indicate that PVST may be performed at the age of 7–12 months for infants vaccinated on 0, 1, and 6-month schedule. To identify non-responders as early as possible, we suggest that PVST is performed at 7 months age or 1 month after the final vaccine dose.

Adherence to multidose Hepatitis B vaccination in a Tertiary Care Centre: A Retrospective Cohort Study

Background: Globally out of 200 crore population who are getting exposed to the hepatitis B virus (HBV),about 350 million are chronically carrying it resulting in 0.5 to 1.2 million deaths each year . These mortalitiesare due to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Horizontal transmission in earlychildhood and parental transmission at any age are the important routes of transmission. This study wasconducted with following objectives.(a) To assess the prevalence of adherence to Hepatitis vaccination.(b) To associate this adherence with demographic factors.Methodology: After receiving approval from the Institutional Ethics Committee a record based retrospectivecohort study was conducted at Gastroenterology and Hepatology OPD of IMS and SUM Hospital,Bhubaneswar. Data regarding all the patients who have received First dose of Hepatitis Vaccine from January2019 to December 2019 were followed up till June 2020 to find out how many of them have revisited toobtain second dose as well as third dose of vaccine. Their demographic characteristics collected from theimmunisation register. Data was entered and analysed using SPSS vs 21 using appropriate statistics.Results and conclusion: Total 1134 subjects have received the first dose of Hepatitis B vaccine. Meanage of the participants is 36±15yrs. First dose taken by 453(39.9%) people, 324(28.6%) had completed theschedule by taking the final dose of vaccine. Hardly one third of the patients adheres to the schedule andcompletes it. Inadequate vaccination makes the patients vulnerable to risks of Hepatitis B and its morbidities.

Design of a Phase III immunogenicity and safety study evaluating two-dose regimens of 9-valent human papillomavirus (9vHPV) vaccine with extended dosing intervals

HPV vaccines are widely licensed as two-dose regimens, 6–12 months apart, for adolescents. Extended intervals between doses may be necessary due to resource constraints or vaccination program disruption. This international, multicenter, open-label study (NCT04708041) will evaluate the safety and immunogenicity of two-dose 9vHPV vaccine regimens with extended intervals of 1–5 years between doses in boys/girls compared with a standard three-dose regimen in women. Participants (planned N = 700) will be enrolled into six cohorts; Cohort 0: boys/girls aged 10–15 years who received one 9vHPV vaccine dose ≥1 year before enrollment without completing the series will receive one study dose of 9vHPV vaccine at day 1; Cohorts 1–4: HPV vaccination-naïve boys/girls aged 9–14 years will receive two doses (day 1 and month 12, 24, 36, or 60); Cohort 5: HPV vaccination-naïve women aged 16–26 years will receive three doses (day 1, months 2 and 6). Primary analyses will be based on serological responses 1 month after final vaccine dose. Co-primary objectives will (1) evaluate non-inferiority of geometric mean titers in each of Cohorts 1–4 versus Cohort 5, and (2) characterize antibody responses in Cohort 0, accounting for the interval between commercial and study vaccine dose. Injection-site and systemic adverse events (AEs) will be collected for 15 days and serious AEs for 12 months post-vaccination; vaccine-related serious AEs and deaths will be collected throughout the study. Results will inform completion of vaccination in individuals who did not complete the recommended series and guide implementation of vaccination programs in resource-limited settings.

Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial

In the absence of a licensed vaccine, Clostridioides (formerly Clostridium) difficile infection represents a substantial health burden. The aim of this study was to evaluate the efficacy, immunogenicity, and safety of a toxoid vaccine candidate. We did a phase 3 multicentre, observer-blind, randomised, controlled trial at 326 hospitals, clinics, and clinical research centres in 27 countries in the USA, Canada, Latin America, Europe, and the Asia-Pacific region. We included adults aged 50 years or older who were considered to be at an increased risk of C difficile infection because they had previously had two hospital stays (each ≥24 h in duration) and had received systemic antibiotics in the previous 12 months (risk stratum 1), or because they were anticipating being admitted to hospital for 72 h or more for elective surgery within 60 days of enrolment (risk stratum 2). Eligible participants were stratified by geographical region and the two risk strata, and randomly assigned (2:1), with a fixed block size of three, to receive either a C difficile toxoid vaccine candidate, containing toxoids A and B (C difficile vaccine candidate group), or a placebo vaccine (placebo group). Participants, investigators, and personnel responsible for collecting safety data and analysing blood and stool samples were masked to group assignment. Personnel responsible for study product preparation and administration were not masked to group assignment. One dose (0·5 mL) of C difficile vaccine candidate or placebo vaccine was administered intramuscularly on days 0, 7, and 30. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection, defined as having three or more loose stools in a period of 24 h or less, loose stools for 24 h or more, and a PCR-positive test for C difficile toxin B in a loose stool sample, within 3 years after the final vaccine dose. The primary outcome was measured in the modified intention-to-treat population (ie, all participants who received at least one injection of the assigned vaccine). The safety of the vaccine was assessed in the safety analysis set (ie, all participants who had received at least one injection, analysed according to the product received). This study is registered with WHO/ICTRP, number U111-1127-7162, and ClinicalTrials.gov, number NCT01887912, and has been terminated. Between July 30, 2013, and Nov 17, 2017, we enrolled and randomly assigned 9302 participants to the C difficile vaccine candidate group (n=6201) or to the placebo group (n=3101). 6173 (99·5%) participants in the C difficile vaccine candidate group and 3085 (99·5%) participants in the placebo group received at least one dose of the vaccine. The study was terminated after the first planned interim analysis because of futility. In the C difficile vaccine candidate group, 34 C difficile infections were reported over 11 697·2 person-years at risk (0·29 infections per 100 person-years [95% CI 0·20-0·41]) compared with 16 C difficile infections over 5789·4 person-years at risk in the placebo group (0·28 infections per 100 person-years [0·16-0·45]), indicating a vaccine efficacy of -5·2% (95% CI -104·1 to 43·5). In the C difficile vaccine candidate group, 2847 (46·6%) of 6113 participants reported an adverse event within 30 days of injection compared with 1282 (41·9%) of 3057 participants in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4·8% in both groups (296 participants in the C difficile vaccine candidate group and 146 participants in the placebo group). 1662 (27·2%) participants in the C difficile vaccine candidate group reported at least one serious adverse event compared with 851 (27·8%) participants in the placebo group. In adults at risk for C difficile infection, a bivalent C difficile toxoid vaccine did not prevent C difficile infection. Since the C difficile vaccine candidate met the criteria for futility, the study was terminated and clinical development of this vaccine candidate was stopped. Sanofi Pasteur.

Functional in vivo characteristics of antibodies generated by an oxycodone vaccine

An oxycodone vaccine (OXY‐sKLH) is being developed to treat opioid use disorder. OXY‐sKLH has been demonstrated to be effective at blocking clinically relevant doses of oxycodone and reducing its reinforcing efficacy. To further assess the potential of OXY‐sKLH for clinical use, critical in vivo properties of the vaccine were studied. Sprague Dawley rats were vaccinated with OXY‐sKLH or control vaccine (sKLH alone) in alum adjuvant. Exposure of vaccinated rats to oxycodone weekly confirmed the expectation that oxycodone alone does not boost oxycodone‐specific antibody titers in vaccinated rats. Re‐vaccination with OXY‐sKLH was necessary to maintain titers. In a separate experiment, antibody titers of vaccinated rats showed a titer of 1.6 × 105 after the final vaccine dose which declined to 0.54 × 105 at 3 months. Vaccine specificity for oxycodone was assessed in vivo. Vaccination protected against oxycodone‐induced, but not methadone‐induced, antinociception. Administration of naloxone to vaccinated rats that had received methadone partially restored nociception and fully reversed respiratory depression. Vaccination of rats with OXY‐sKLH did not alter the pharmacokinetics or antinociception of subsequently administered fentanyl. These in vivo data confirm the previously reported in vitro specificity of this vaccine for oxycodone. Finally, vaccination with OXY‐sKLH extended oxycodone’s half‐life from 0.75 hr in control rats to 24 hr. Taken together, these results indicate that antibody titers generated by OXY‐sKLH are long lasting, and will not interfere with clinically useful non‐targeted opioids, and will decline even in the face of continued oxycodone exposure unless boosted by re‐vaccination. The prolonged oxycodone half‐life in vaccinated rats suggests the potential for antibody saturation if oxycodone exposure continues and is substantial and persistent.Support or Funding InformationThis work was supported by the National Institutes of Health National Institute on Drug Abuse [Grant U01DA038876] (to M.P. and P.R.P.)

Immunogenicity and safety of different dosing schedules of trivalent inactivated influenza vaccine in pregnant women with HIV: a randomised controlled trial

SummaryBackgroundStandard-dose, seasonal, trivalent, inactivated influenza vaccine induces moderate-to-low haemagglutination-inhibition antibody responses in people living with HIV. This study assessed the immunogenicity and safety of different dosing schedules of inactivated influenza vaccine in pregnant women living with HIV in South Africa.MethodsIn this double-blind, randomised, controlled trial, we recruited pregnant women with HIV from seven antenatal clinics in Soweto, South Africa. Pregnant women were eligible if they were aged 18–38 years, infected with HIV, and had an estimated gestational age of 12–36 weeks. Women were randomly assigned (1:1:1), using a computer-generated randomisation list, to receive inactivated influenza vaccine containing 15 μg of each of the three seasonal influenza strains for that year, as a single dose, a double dose, or two single doses 1 month apart. Participants and study personnel were masked to group allocation. Haemagglutination-inhibition antibody responses were measured for all groups in the mothers at enrolment and at 1 month after each vaccine dose, and in the single-dose and double-dose groups within 7 days of birth in the neonates. Immunogenicity analyses only included women with visits 28–35 days apart and infants who were born at least 28 days after maternal immunisation. The primary was seroconversion rate to each of the vaccine strains in the mothers 1 month after completion of the dosing schedule, and the primary safety outcomes were frequency of local and systemic reactions. Safety was assessed in mothers and infants until 24 weeks post partum and analysed in all participants who received at least one dose of vaccine. This study is registered with ClinicalTrials.gov, NCT01527825, and is closed to accrual.FindingsBetween Feb 11, and June 6, 2013, 800 pregnant women living with HIV were enrolled and randomly assigned to the single-dose (n=266), double-dose (n=265), or two-single-doses (n=269) group. In the analysable population, seroconversion rates in mothers 1 month after the final vaccine dose were significantly higher in the double-dose group (n=230; ranging from 29% to 65% for the three vaccine strains) than in the single-dose group (n=230; ranging from 18% to 49%; p≤0·019 for the three vaccine strains), but were similar between the two-single-doses group (n=220; ranging from 23% to 52%) and the single-dose group (p≥0·20 for the three vaccine strains). Safety outcomes were similar in the three groups, except for more injection-site reactions in recipients in the double-dose group.InterpretationA regimen of double-dose inactivated influenza vaccine gave slightly greater immunogenicity than did a single-dose regimen in pregnant women living with HIV. However, immunogenicity in the double-dose group was still lower than historical data from the same setting in pregnant women without HIV. More immunogenic vaccines are needed for pregnant women living with HIV to enhance transplacental transfer of vaccine-induced protective antibodies to their newborn infants.FundingBill & Melinda Gates Foundation.

Efficacy and long-term durability of intradermal recombinant hepatitis B virus vaccine among intramuscular vaccine nonresponders: A prospective study in healthcare personnel.

Data on efficacy, safety, and durability of intradermal vaccine administration in persons who have not responded appropriately to intramuscular administration of hepatitis B virus (HBV) vaccine are relatively scarce. We designed a prospective case series in an urban tertiary care hospital in Israel. The medical records of 4007 healthcare personnel who had worked in the hospital between 1996 and 2006 were examined and those with an unsatisfactory level (<10 mIU/ml) of hepatitis B surface antibody (HBsAb) following two courses of a three-dose intramuscular HBV vaccine ("nonresponders") were identified. Nonresponders were vaccinated with three doses of 5 µg of intradermal recombinant hepatitis B surface antigen-based vaccine at weeks 0, 2, and 4. Level of HBsAb was determined 4 weeks after the last dose, and an additional dose was administered as needed. HBsAb level was again determined 24 weeks after the final vaccine dose to assess late immune reactivity and long-term durability of the vaccine. Vaccine safety was assessed at each vaccination and testing session. Twenty-seven subjects were included in the study, and 21 completed the study. The proportion of subjects with satisfactory HBsAb level at 4 weeks after the last administered dose was 70.3% (19/27). The proportion of subjects with sustained immune response at 24 weeks was 62.9% (17/27) according to intention-to-treat analysis and 80.9% (17/21) according to per protocol analysis. There were no reports of adverse events in response to the administration of the vaccine. Intradermal administration of HBV vaccine offers an efficient, safe, and durable option for intramuscular vaccine nonresponders and represents a means to optimize utilization of the widespread HBs antigen-based vaccine formulation.

Outreach Hepatitis B Vaccination of Female Sex Workers in Central-West Brazil

To evaluate the hepatitis B immunization status of female sex workers (FSWs) in Central-West Brazil and to evaluate their compliance with and immune response to hepatitis B vaccination delivered using outreach strategies. A total of 721 FSWs recruited in 2 large cities in Central-West Brazil were interviewed and screened for the presence of hepatitis B virus (HBV) markers. Hepatitis B vaccine was offered to all women susceptible to HBV, using outreach strategies. The immune response of FSWs who received a full course of vaccine was assessed following the final vaccine dose. We found that 27.6% of FSWs, the majority of whom were aged 18 to 25 years, had serological evidence of previous hepatitis B vaccination. A total of 434 FSWs were eligible for vaccination, 389 (89.6%) of whom accepted the first hepatitis B vaccine dose. Of those, 64% received a second dose and 37.5% received all three doses. Through the outreach strategy, there was a 52.2% increase in the number of women who received the second dose and a 67% increase in the number who received the third dose. Of the 146 women who received a full course of vaccine, 105 accepted testing for quantitative anti-HBs (hepatitis B surface antibody) following the final vaccine dose, and 92.4% of those tested had developed protective levels of anti-HBs. Lower education level, workplace, and length of prostitution were predictors of full-vaccine acceptance. The present findings illustrate the benefits of using outreach strategies to overcome the difficulties of vaccinating hard-to-reach populations such as FSWs.

A double-dose hepatitis B vaccination schedule in travelers presenting for late consultation.

Vaccination against hepatitis B virus (HBV) is recommended for all travelers visiting HBV-endemic countries. However, travelers often present with insufficient time for the standard HBV vaccine schedule (SVS). We examined seroprotection against HBV following an alternative two-visit vaccination schedule (TVS) with currently available vaccine products, and completion rates with this TVS. A retrospective cohort study was conducted in three travel clinics in British Columbia, Canada. Adults ≥20 years old traveling to an HBV-endemic country, and unable to complete the standard or rapid HBV vaccination schedule before departure, were offered a TVS that consisted of a double dose of HBV vaccine at day 0, followed by a single dose in 4 to 12 months. Immunity to HBV [anti-HBV surface antigen (HBs) ≥10 mIU/mL] was determined 1 to 6 months following the final dose of HBV vaccine. Logistic regression modeling was used to assess correlates of seroprotection. We also determined completion rate with this TVS at two clinics. In total, 117 participants (age range, 21-81 years, median age 57) met the inclusion criteria. Of these, 97 (82.9%) were immune after the TVS. Immunity was demonstrated in 93.1% of patients <50 years old and 79.5% of patients ≥50 years old. Increasing age was associated with reduced odds of developing immunity to HBV using the TVS [adjusted odds ratio = 0.954, 95% confidence interval (CI): 0.904, 1.008]. The completion rate of the TVS was 32.6% over a 12-month period. Completion rates varied between clinics (23.5% vs 48.4%, p < 0.001), suggesting that clinic-specific follow-up policies were important. Seroprotection with completion of this TVS was similar to or exceeded that published in the literature for the SVS by age. However, even with a TVS, completion rates were low, underscoring the importance of follow-up. Further research is needed to determine whether travelers are protected prior to completion of this TVS.

Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women

PurposeAnnually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated. MethodsData were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response. ResultsA total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10mIU/mL included gestational age <37 weeks, vaccine birth dose >12h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs <10mIU/mL; the proportion increased from 2% at 1–2 months to 21.6% at 15–16 months after the final dose. Receipt of a 4th dose improved the response rate (OR=0.5, CI=0.3, 0.8). ConclusionsNinety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1–2 months of final vaccine dose to avoid unnecessary revaccination.

Association of Childhood Pertussis With Receipt of 5 Doses of Pertussis Vaccine by Time Since Last Vaccine Dose, California, 2010

In 2010, California experienced its largest pertussis epidemic in more than 60 years; a substantial burden of disease was noted in the 7- to 10-year-old age group despite high diphtheria, tetanus, and acellular pertussis vaccine (DTaP) coverage, indicating the possibility of waning protection. To evaluate the association between pertussis and receipt of 5 DTaP doses by time since fifth DTaP dose. Case-control evaluation conducted in 15 California counties. Cases (n = 682) were all suspected, probable, and confirmed pertussis cases among children aged 4 to 10 years reported from January through December 14, 2010; controls (n = 2016) were children in the same age group who received care from the clinicians reporting the cases. Three controls were selected per case. Vaccination histories were obtained from medical records and immunization registries. Primary outcomes were (1) odds ratios (ORs) for the association between pertussis and receipt of the 5-dose DTaP series and (2) ORs for the association between pertussis and time since completion (<12, 12-23, 24-35, 36-47, 48-59, or ≥60 months) of the 5-dose DTaP series. Logistic regression was used to calculate ORs, accounting for clustering by county and clinician, and vaccine effectiveness (VE) was estimated as (1 - OR) × 100%. Among cases and controls, 53 (7.8%) and 19 (0.9%) had not received any pertussis-containing vaccines, respectively. Compared with controls, children with pertussis had a lower odds of having received all 5 doses of DTaP (OR, 0.11; 95% CI, 0.06-0.21 [estimated VE, 88.7%; 95% CI, 79.4%-93.8%]). When children were categorized by time since completion of the DTaP series, using an unvaccinated reference group, children with pertussis compared with controls were less likely to have received their fifth dose within the prior 12 months (19 [2.8%] vs 354 [17.6%], respectively; OR, 0.02; 95% CI, 0.01-0.04 [estimated VE, 98.1%; 95% CI, 96.1%-99.1%]). This association was evident with longer time since vaccination, with ORs increasing with time since the fifth dose. At 60 months or longer (n = 231 cases [33.9%] and n = 288 controls [14.3%]), the OR was 0.29 (95% CI, 0.15-0.54 [estimated VE, 71.2%; 95% CI, 45.8%-84.8%]). Accordingly, the estimated VE declined each year after receipt of the fifth dose of DTaP. Among children in 15 California counties, children with pertussis, compared with controls, had lower odds of having received the 5-dose DTaP series; as time since last DTaP dose increased, the odds increased, which is consistent with a progressive decrease in estimated vaccine effectiveness each year after the final dose of pertussis vaccine.

Evaluation of meningococcal serogroup C conjugate vaccine programs in Canadian children: Interim analysis

BackgroundTo assess antibody titers afforded by meningococcal C- (MenC) tetanus toxoid conjugate vaccine at 12 months of age in three different immunization schedules. MethodsThis prospective study included three similar cohorts of healthy infants from 1-dose, 2-dose and 3-dose MenC infant immunization programs. Infants were enrolled at 12 months of age and given the final scheduled dose of MenC-tetanus toxoid conjugate vaccine with sera collected prior to and 1 month after the vaccination. Serum bactericidal activity (SBA) titers≥1:8 were considered protective. ResultsBefore the 12 month dose, participants had significantly different protective titers according to the number of prior doses received: 100% (95% CI 97.6–100%) of infants who had 2 prior doses (at 2 and 4 months) were protected compared to 84.0% (76.7–89.3%) of participants with one dose (at 2 months) and 27.6% (21.0–35.4%) of unvaccinated infants. All subjects were protected after the 12 month MenC dose, but titers were higher with prior priming. ConclusionsTwo MenC doses given in infancy afford optimal protection during the first year of life; however, substantial protection was seen after one dose at 2 months.