bluuebunny/crossref_metadata_2025_split huggingface dataset:
2. Understanding Patient Preferences for Meningococcal Serogroup B Vaccines in the United States
Authors: Johnson Reed , Fairchild Angelyn , Whittington Dale , Presa Jessica , Srivastava Amit , Huang Liping 
Published: January 2021

Abstract

Background
Among US adolescents, meningococcal disease serogroup B (MenB) causes more cases (62% in 2018) than other 4 serogroups (A, C, W, Y). ACIP’s recommendation for shared clinical decision-making calls for individuals to be given the choice of vaccination after consultation with their health care provider. No data are available to-date that formally quantify values and preferences for MenB vaccines. Our objective is to quantify such values.

Methods
Following best-practice standards for stated-preference research, a survey employed a discrete choice experiment (DCE) and contingent-valuation (CV) questions to quantify respondents’ trade-off preferences for vaccines that protect against diseases with various levels of severity and incidence, and to estimate the monetary value of receiving additional consultation regarding MenB vaccination with healthcare providers. A total of 2162 respondents (1203 young adults and 1185 parents) completed on-line surveys between August - October 2019.

Results
DCE analysis identified 3 classes of respondents for parents (table 1) and young adults, respectively. Overall, half of the respondents considered vaccines for low-incidence, high-severity diseases such as MenB to be at least as important as vaccines for high-incidence, low- severity diseases.
Respondents were asked to react to a hypothetical situation in which the health care provider did not discuss MenB vaccines with them and found out later. Approximately 70% of respondents expressed reactions ranging from ‘Concerned’ to ‘Angry or Disgusted’ (Figure 1). The majority of young adults and parents wanted physician-provided information about protection against low-incidence but serious diseases such as MenB.
The CV analysis estimated that willingness to pay for the MenB vaccine was about US$300 for young adults and over US$400 for parents. However, they often felt entitled to the consultation with their health care provider about the MenB vaccines and were not willing to pay much for it (Figure 2).
Table 1. Parent Class Results (n=1185)

Figure 1. Respondents’ Reactions to Health Care Provider Choosing Not to Discuss the MenB Vaccine with Them

Figure 2. Mean Willingness to Pay for Additional Time with Doctor for Discussing MenB Vaccine and Willingness to Pay for MenB Vaccine

Conclusion
The study found that parents of adolescents and young adults placed significant value on obtaining information about and protection against low-incidence diseases such as MenB that can result in severe long-term disabilities and death.

Disclosures
Reed Johnson, PhD, Pfizer (Research Grant or Support) Angelyn Fairchild, BA, Pfizer (Research Grant or Support) Dale Whittington, PhD, Pfizer (Research Grant or Support) Jessica Presa, MD, Pfizer (Employee) Amit Srivastava, PhD, Pfizer (Employee) Liping Huang, MD, MA, MS, Pfizer (Employee)
4. MenACWY-TT Long-Term Antibody Persistence Following Adolescent Vaccination and Evaluation of a Booster Dose: A Review of Clinical Data
Authors: Peyrani Paula , Webber Chris , Burman Cindy , Balmer Paul , Perez John L 
Published: January 2021

Abstract

Background
A peak in meningococcal carriage and invasive meningococcal disease (IMD) occurs during adolescence and young adulthood. In the United States, preventive vaccination with a quadrivalent meningococcal (MenACWY) conjugate vaccine is recommended at age 11–12 years, with a booster dose given at age 16 years. MenACWY-TT (Nimenrix®), a MenACWY tetanus toxoid conjugate vaccine, was first licensed in 2012 and is available in the European Union and 50 other countries. Immune responses to other MenACWY conjugate vaccines decline over several years following vaccination. Here, we review 2 recent studies evaluating the long-term persistence of MenACWY-TT immune responses in adolescents as well as safety and immunogenicity of a booster dose given 10 years after primary vaccination.

Methods
Both studies (ClinicalTrials.gov NCT01934140, NCT03189745) were extensions of phase 2 or 3 studies of subjects 11–17 years of age given a single dose of MenACWY-TT or MenACWY polysaccharide vaccine (MenACWY-PS). Immune responses through 10 years after primary vaccination and after a Year 10 MenACWY-TT booster dose were measured by serum bactericidal antibody assays using baby rabbit complement (rSBA). Specific endpoints included percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and geometric mean titers (GMTs). Booster dose safety and tolerability were also evaluated.

Results
In both studies, the percentages of subjects with rSBA titers ≥1:8 through 10 years postvaccination were generally higher or similar among MenACWY-TT (69.3%–91.2% at Year 10; n=137–163) compared with MenACWY-PS (24.4%–88.9%; n=45–53) recipients for all 4 serogroups (Figure); similar results were observed for GMTs (146.0–446.9 vs 12.9–191.0 at Year 10). One month after a MenACWY-TT booster dose, 97.7%–100% of subjects across groups had titers ≥1:8 (Figure), and GMTs were markedly higher than prebooster values. No new safety signals were identified following the booster dose.
Figure 1. Subjects in each of the 2 studies with rSBA titers ≥1:8 before and at 1 month, 5 years, and 10 years after primary vaccination with MenACWY-TT or MenACWY-PS at 11–17 years of age and 1 month after booster vaccination with MenACWY-TT at 10 years following primary vaccination.

Conclusion
Functional antibodies for all 4 serogroups persisted through 10 years after MenACWY-TT adolescent vaccination, suggesting that this vaccine may help prevent IMD throughout the lengthy risk period in this group. A MenACWY-TT booster dose may further extend protection regardless of the primary vaccine received.
Funded by Pfizer.

Disclosures
Paula Peyrani, MD, Pfizer Inc (Employee, Shareholder) Chris Webber, MD, Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Paul Balmer, PhD, Pfizer Inc (Employee, Shareholder) John L. Perez, MD, MA, Pfizer Inc (Employee, Shareholder)
10. Kinetics of Post-Vaccination Seroprotection to S. Pneumonia for the Immune-Compromised and Vaccine-Naïve Populations
Authors: Gruenglas Jeffrey , Mond James , Scobie Micaela , Tolman Cynthia , Martinez Joseph 
Published: January 2021

Abstract

Background
S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization.

Methods
Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine.

Results
There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached.
OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2.

OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2.

Conclusion
Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies.

Disclosures
All Authors: No reported disclosures
11. Missed Vaccine Opportunities During the COVID-19 Pandemic
Authors: Shallal Anita , Vahia Amit T , Kenney Rachel , Weinmann Allison J 
Published: January 2021

Abstract

Background
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for all adults over the age of 65 to reduce S. pneumoniae pneumonia. Our institution follows a standing order for nurses to vaccinate adults who meet the Advisory Committee on Immunization Practices (ACIP) criteria. During the COVID-19 pandemic surge, the pneumococcal vaccine and influenza vaccine nurse-driven protocol was determined to be non-essential on 3/23, and 4/2 respectively. Our study aims to characterize missed vaccine opportunities among patients hospitalized with COVID-19 during this surge.

Methods
A retrospective cross-sectional study of PCR-positive COVID-19 patients admitted to an inner-city hospital and discharged alive between the dates of 3/23 and 4/21/2020. Patients under the age of 65 were excluded. Data collected included patient age, gender, race, length of stay, co-morbidities that would indicate a vaccine opportunity, prior vaccinations, and whether there was a vaccine opportunity for PPSV23 and influenza defined by ACIP indications. Vaccine history was evaluated using the electronic medical record (EMR) and Michigan Care Improvement Registry. If there was a vaccine opportunity, we documented whether a vaccine was given before hospital discharge. Total numbers of vaccines given for time periods in 2019 and 2020 were collected from EMR for comparison.

Results
100 patients over the age of 65 were included. The average age was 72.8 years, and most patients (66%) were of African American race. The mean length of stay was five days. 52 patients were identified as having an opportunity to receive PPSV23, and 0 patients received the vaccine. 67.3% had more than one indication for PPSV23. 37 patients were eligible to receive influenza vaccine, and 0 received the vaccine. Results are summarized in table 1. Figures 1 and 2 display the number of pneumococcal and influenza vaccines given per EMR, respectively.
Figure 1

Figure 2

Table 1

Conclusion
Due to prioritization of potential staffing shortages and clustering nursing care, an opportunity to vaccinate patients with pneumococcal and influenza vaccines was missed. It is important for health care providers to be aware of this potential opportunity for vaccination of high-risk patients in order to promote primary prevention in future waves of pandemics.

Disclosures
All Authors: No reported disclosures
12. Randomized Studies of Two Clostridioides (Clostridium) difficile Vaccine Formulations
Authors: Lawrence Jody , Kitchin Nicholas , Anderson Annaliesa S , Pride Michael W , Jansen Kathrin U , Gruber William C , Peng Yahong , Yi Kevin , Knirsch Charles , Webber Chris 
Published: January 2021

Abstract

Background
Two formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) were assessed for safety and immunogenicity in randomized studies in healthy adults 50–85 years of age.

Methods
The Phase 1 study of QS-21 adjuvanted toxoid vaccine randomized subjects 3:1 to 100 μg QS-21-containing C difficile vaccine or placebo; 3 doses were given according to 2 different schedules: a shortened month (Months 0, 1, 3) or day (Days 1, 8, 30) regimen. The Phase 2 toxoid-alone vaccine study randomized subjects 3:3:1 to receive 100 or 200 μg unadjuvanted C difficile vaccine formulation or placebo in Stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3. Three doses were given on a day (Days 1, 8, 30) regimen. Safety was the primary outcome for both studies. Immunogenicity was determined by measuring serum toxin A– and B–specific neutralizing antibodies.

Results
In the day regimen, 10 reports across both studies of grade 3 injection site redness postdose 2 triggered predefined stopping rules. Local reactions in both studies were more common among vaccine versus placebo recipients. Injection site pain predominated and was generally mild in severity. Systemic events were infrequent and generally mild-to-moderate in severity. Adverse events were reported by 50.0%–75.0% and 16.7%–50.0% of subjects in the QS-21 and toxoid-alone studies, respectively. Immune responses peaked around Day 37 (shortened-month regimen) or between Day 15 and Month 2 (day regimen), and remained above baseline throughout follow-up.

Conclusion
Both formulations demonstrated robust immunogenicity. However, both studies stopped early due to grade 3 injection site redness postdose 2 of the day (Days 1, 8, 30) regimen; neither formulation progressed to later stage development. Instead, an aluminum hydroxide-containing formulation of the vaccine candidate administered at 0, 1, and 6 months, which was safe and immunogenic in phase 1 and 2 studies, advanced to phase 3 studies.

Disclosures
Jody Lawrence, MD, Pfizer, Inc (Employee) Nicholas Kitchin, MD, Pfizer, Inc (Employee) Annaliesa S. Anderson, PhD, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Charles Knirsch, MD, Pfizer (Employee) Chris Webber, MD, Pfizer Inc (Employee, Shareholder)
20. Cost-Effectiveness of Implementing 13-Valent Pneumococcal Conjugate Vaccine (Pcv13) for Adults Aged ≥19 Years with Underlying Conditions
Authors: Kobayashi Miwako , Stoecker Charles , Xing Wei , Cho Bo-Hyun , Pilishvili Tamara 
Published: January 2021

Abstract

Background
In June 2019, the U.S. Advisory Committee on Immunization Practices changed the recommendation for routine PCV13 use in immunocompetent adults aged ≥65, including those with certain chronic medical conditions (CMC); PCV13 is now recommended based on shared clinical decision-making. Adults with CMC continue to be at increased risk for pneumococcal disease. We assessed the cost-effectiveness of adding PCV13 to the recommended PPSV23 dose for adults aged ≥19 years with CMC.

Methods
We used a probabilistic model following a cohort of 19-year-old U.S. adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$] using the societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. Table 1 shows vaccine effectiveness (VE) assumptions for the base case. We performed one-way sensitivity analyses assuming higher PCV13 VE against serotype 3 disease.
Vaccine effectiveness assumptions by age group used for the base case

Results
In the base-case scenario, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY. Results of one-way sensitivity analyses are presented in Table 2.
Base case and one-way sensitivity analyses of adding PCV13 at diagnosis of CMC

Conclusion
Adding PCV13 in series with PPSV23 for adults 19 years or older with CMC was not cost-saving. Results were sensitive to assumptions on PCV13 VE against serotype 3 disease.

Disclosures
All Authors: No reported disclosures
21. Current and Nadir CD4+ Counts Are Associated with Heplisav-B Seroprotection Rates in People with HIV
Authors: Schnittman Samuel , Zepf Roland , Cocohoba Jennifer , Sears David 
Published: January 2021

Abstract

Background
A two-dose hepatitis B (HBV) vaccine with an immunostimulatory adjuvant (HBV-ISS, Heplisav-B), was FDA approved in 2017 for adults 18 years and older. In randomized controlled trials (RCTs), HBV-ISS demonstrated a seroprotection rate (SPR) of 90–95% versus 65–80% for Engerix-B (HBV-Eng). No RCTs, however, included people with HIV (PWH), and the SPR and its predictors in this population are unknown.

Methods
This retrospective cohort study enrolled PWH ages 18 years and older without current HBV seroprotection at an HIV clinic at a tertiary care center. HBV seroprotection was defined as an anti-HBV surface antibody level &gt;= 10 mIU/mL. Patients without follow-up titers after immunization were excluded. The primary outcome was the SPR, the proportion of patients with HBV seroprotection at any point following the first HBV-ISS vaccination.

Results
Among the 51 PWH included, 50 received 2 doses of HBV-ISS (1 patient who received 1 dose developed seroprotection) (Table 1). Median time to antibody titer measurement was 11 weeks (IQR 7–19 weeks). Median age was 59 years, 90% were men, and 96% had VL &lt; 200. There were no pregnant or breastfeeding patients. The SPR was 82% (42/51) in the cohort, and 86% (38/44) when patients with significant non-HIV immunosuppression (decompensated cirrhosis, solid organ transplantation, active chemotherapy) were excluded. There were no significant differences in SPR based on age, sex, BMI, diabetes mellitus, chronic kidney disease, history of remote anti-HBV surface or core antibody positivity, or prior HBV vaccination (Table 2). Lower current and nadir CD4+ counts were associated with progressively lower SPRs (P for trend &lt; 0.0001 for both) (Figure 1).
Table 1. Baseline Demographics and Characteristics

Table 2. Seroprotection Rate (SPR) by Variables of Interest

Figure 1. Seroprotection Rate (SPR) by Current and Nadir CD4+ Count

Conclusion
The SPR from HBV-ISS in PWH appears comparable to the immunocompetent patients included in RCTs, especially when patients with significant non-HIV immunosuppression are excluded. The SPR demonstrated in this single-arm, retrospective study was higher than that of HBV-Eng in immunocompetent patients, and consideration should be given to establishing HBV-ISS as first-line HBV vaccination in PWH. Finally, SPR is significantly reduced in those with lower current and nadir CD4+ counts. Further research on the effectiveness of a repeat vaccination series or higher dosing in these subgroups is needed.

Disclosures
Jennifer Cocohoba, PharmD, AAHIVP, BCPS, Viiv (Grant/Research Support)
22. Description of Hospitalized Patients with Influenza Vaccine Failure
Authors: Kimball Joanna , Zhu Yuwei , Wyatt Dayna , Talbot Helen 
Published: January 2021

Abstract

Background
Despite influenza vaccination, some patients develop illness and require hospitalization. Many factors contribute to vaccine failure, including mismatch of the vaccine and circulating strains, waning immunity, timing of influenza season, age and patient comorbidities such as immune function. This study compared vaccinated, hospitalized patients with and without influenza.

Methods
This study used 2015–2019 Tennessee data from the US Hospitalized Adult Influenza Vaccine Effectiveness Network database. Enrolled patients were ≥ 18 years vaccinated for the current influenza season and admitted with an acute respiratory illness. Patient or surrogate interviews and medical chart abstractions were performed, and influenza vaccinations were confirmed by vaccine providers. Influenza PCR testing was performed in a research lab. Statistical analyses were performed with STATA and R using Pearson’s chi-squared, Kruskal-Wallis and Wilcoxon rank-sum tests and multivariate logistic regression.

Results
1236 patients met study criteria, and 235 (19%) tested positive for influenza. Demographics, vaccines and comorbidities were similar between the two groups (Table 1) except for morbid obesity, which was more common in influenza negative patients (13% vs 8%, p = 0.04), and immunosuppression, which was more common in the influenza positive (63% vs 54%, p = 0.01). Logistic regression analysis demonstrated older patients (OR 1.47, 95% CI 1.03–2.10) and immunosuppressed patients (OR 1.56, 1.15–2.12) were at increased risk for influenza (Table 2 and Figure 1). Immunosuppression also increased the risk for influenza A/H3N2 (OR 1.86, 95% CI 1.25–2.75). A sensitivity analysis was performed on patients who self-reported influenza vaccination for the current season without vaccine verification and demonstrated increased risk of influenza in older adults (OR 1.66, 95% CI 1.16–2.39).
Table 1: Demographics of influenza positive versus influenza negative patients in influenza vaccinated, hospitalized patients.

Table 2: Logistic regression analyses of vaccinated, hospitalized influenza positive patients; vaccinated, hospitalized patients with influenza A subtypes and self-reported vaccinated, hospitalized influenza positive patients.

Figure 1: Predicted Probability of Hospitalization with Influenza, Influenza A/H1N1 and Influenza A/H3N2 in Vaccinated Patients by Age.

Conclusion
Our study demonstrated an increased risk of influenza vaccine failure in older patients and immunosuppressed patients. These groups are also at increased risk for influenza complications. To improve protection of these patients against future influenza illnesses, more effective vaccines are needed, and more research on ring vaccination should be pursued.

Disclosures
All Authors: No reported disclosures