bluuebunny/crossref_metadata_2025_split huggingface dataset:
2706. Indirect Effects of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Adults in British Columbia, Canada
Authors: Vadlamudi Nirma K , Patrick David , Hoang Linda , Marra Fawziah 
Published: October 2019

Abstract

Background
Many jurisdictions report a significant reduction in invasive pneumococcal disease (IPD) in adults following implementation of the pneumococcal conjugate vaccines, 7-valent (PCV7) and 13-valent (PCV13) in childhood immunization programs. This study evaluates the indirect effect of conjugate vaccines on IPD in British Columbia, Canada over a 14 year period (2002–2015).

Methods
Using provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in adults 18 years of age and older. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.

Results
A total of 3793 cases were reported over the 14 year period. The overall annual incidence increased from 4.32 cases per 100,000 population in 2002 to 8.61 cases per 100,000 population in 2015. Overall, IPD has increased by 80% (IRR: 1.80; 95% CI: 1.59–2.04) compared with baseline, especially in adults ≥ 85 years of age (PCV13 vs baseline: IRR: 1.90; 95% CI: 1.25–03.05). This increase was the highest after introduction of PCV7 (IRR: 1.87; 95% CI: 1.65–2.11); the incremental change after introduction of PCV13 was non-significant (IRR 0.96; 95% CI: 0.90–1.03). While PCV7 type IPD plummeted by 76% (IRR 0.24; 95% CI: 0.18–0.31) since introduction of PCV7 compared with baseline, a modest decline in PCV13 type IPD of 20% was seen (IRR 0.80; 95% CI: 0.71–0.89) since introduction of PCV13.

Conclusion
Although PCV7-type IPD has decreased substantially, only a modest reduction in IPD from the additional 6 serotypes in the PCV13 vaccine was observed.

Disclosures
All authors: No reported disclosures.
2717. The Impact of Pneumococcal Conjugate Vaccine in Nonbacteremic Pneumococcal Pneumonia Among Cancer Patients
Authors: Lee Yeon Joo , Richards Rocco , Su Yiqi , Kaltsas Anna , Papanicolaou Genovefa 
Published: October 2019

Abstract

Background
Invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NB-PNA) are associated with substantial morbidity and mortality in cancer patients. IPD incidence among cancer patients at MSKCC sharply declined after the introduction of routine childhood immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) (1). An indirect effect of PCV on pneumococcal pneumonia incidence has also been reported (2, 3). The impact of PCV on the incidence of NB-PNA in patients with cancer has not been well studied.

Methods
Retrospective review of patients treated at MSKCC, 1993–2012. Unique patient visits (UPV) per year were defined as ≥1 inpatient or outpatient encounter within one calendar year. NB-PNA was defined as Isolation of Streptococcus pneumoniae from sputum or bronchoalveolar lavage (BAL); with associated symptoms (cough, sputum production, and/or fever) and radiographic findings compatible with pneumonia on chest radiograph or computerized chest tomography. NB-PNA incidence was calculated as number of NB-PNA cases per 1000 UPV. Three-time periods were examined: “before PCV7” (1993–2000), “after PCV7” (2001–2010), “after PCV13” (2011–2012).

Results
Of 323 NB-PNA cases, S. pneumoniae was isolated from BAL in 64 (20%) and sputum in 259 (80%). 182 (56%), 121 (37%), and 20 (7%) NB-PNA cases occurred “before PCV7,” “after PCV7,” and “after PCV13,” respectively. The incidence of NB-PNA was highest in patients with hematologic malignancies and in patients ≥65 years during all three periods (Table 1). NB-PNA incidence was lower “after PCV7” compared with “before PCV7” (0.47 vs. 0.13, P < 0.001). A non-statistically significant lower incidence of NB-PNA was noted “after PCV13” vs. “after PCV7” (0.13 vs. 0.09, P = 0.19). The highest decline of NB-PNA after PCV7 introduction was observed in patients ≥65 years (0.67 vs. 0.16, P < 0.001).

Conclusion
(1) The incidence of NB-PNA in adult cancer patient declined after PCV7 compared with before PCV7. (2) The reduction in NB-PNA was highest in patients ≥65 years suggesting an indirect effect from PCV7 childhood immunization. (3) A trend toward decreased incidence in NB-PNA was noted after PCV13; further surveillance is required to ascertain this trend.

Disclosures
All authors: No reported disclosures.
2724. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Healthy Meningococcal Vaccine-Naïve Children (2–9 Years)
Authors: Simon Michael W , Brandon Donald , Christensen Shane , Baccarini Carmen , Jordanov Emilia , Dhingra Mandeep S 
Published: October 2019

Abstract

Background
MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in individuals 6 weeks of age and older. We evaluated the safety and immunogenicity of MenACYW-TT compared with a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-CRM [Menveo®]) in US children 2–9 years of age.

Methods
In a modified double-blind Phase III study (NCT03077438), 1000 children were randomized to receive one dose of either MenACYW-TT vaccine or MenACWY-CRM vaccine. Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure antibodies against representative meningococcal serogroup strains at baseline and 30 days after vaccination. Safety data were collected up to 6 months post-vaccination.

Results
Non-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated for MenACYW-TT compared with MenACWY-CRM at Day 30 compared with baseline. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-CRM administration for all four serogroups (A: 86.4% vs 79.3%; C: 97.8% vs 67.1%; W: 94.8% vs 86.3%; Y: 98.5% vs 90.8%). Similar results were observed in two age substrata (2 to 5 years and 6 to 9 years). Percentages of participants with post-vaccination rSBA titers ≥ 1:128 were comparable between both groups. The safety profiles of MenACYW-TT and MenACWY-CRM were comparable. Reactogenicity at the MenACYW-TT injection site was lower than at the MenACWY-CRM injection site. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study.

Conclusion
MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with that for the licensed MenACWY-CRM vaccine when administered as a single dose to meningococcal vaccine-naïve children.

Disclosures
All authors: No reported disclosures.
2727. Numbers Needed to Vaccinate for Prevention of Adult Pneumonia with Pneumococcal Conjugate Vaccine: Which Values Should Determine Policy?
Authors: Gessner Bradford D , Isturiz Raul E , Snow Vincenza , Jodar Luis 
Published: October 2019

Abstract

Background
At the meeting of the Advisory Committee on Immunization Practices (ACIP) on February 28, 2019, the US Centers for Disease Control and Prevention (CDC) and the Pneumococcal Work Group (PWG) presented data to inform the public health question of whether the 13-valent pneumococcal conjugate vaccine (PCV13) should continue to be recommended for routine immunization of all adults age 65 years and older in the United States.

Methods
We reviewed all three available studies reporting adult PCV13 vaccine effectiveness against all-cause pneumonia, calculated numbers needed to vaccinate (NNV), and compared these results to NNV data presented to the ACIP based on etiologically and radiologically confirmed vaccine-type (VT) disease. Studies included a randomized controlled trial of inpatient pneumonia among Dutch persons age 65+ years, a US CDC-led observational study among the US Medicare population of inpatient pneumonia, and an observational study of inpatient and outpatient pneumonia in Germany.

Results
Based on a background incidence of etiologically and radiologically confirmed VT community-acquired pneumonia of 17–76 per 100,000 per year and PCV13 VE of 43%, the CDC presented to ACIP an annual NNV estimate for preventing one pneumonia case of 3,000 to 14,000. For the three studies we reviewed, VEs were 6% to 12% against all-cause pneumonia and background all-cause pneumonia incidences were 891 to 1776 per 100,000 per year. Assuming a 5-year PCV13 duration of protection, for these three studies NNVs to prevent a case of pneumonia were 95 to 277, or 11- to 147-fold lower than what was presented at ACIP.

Conclusion
To avoid inaccurate conclusions for potentially efficient interventions, calculations of NNVs, rate reductions, and economic benefits should include sensitive outcomes, such as all-cause pneumonia, in addition to more specific but lower sensitivity outcomes such as VT, radiologically confirmed pneumonia.

Disclosures
All authors: No reported disclosures.
2722 B. Efficacy and Safety of a Booster Dose of the MenACWY-TT Vaccine Administered 10 Years After Primary Vaccination with MenACWY-TT or MenACWY-PS
Authors: Quiambao Beatriz , Peyrani Paula , Webber Chris , Van Der Wielen Marie , Bianco Veronique , Perez John L , Cutler Mark W , Li Ping 
Published: October 2019

Abstract

Background
The quadrivalent meningococcal ACWY polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix) is licensed in various countries to prevent disease caused by meningococcal serogroups A, C, W, and Y. In a previous study (NCT00464815), subjects aged 11‒17 years received a primary dose of MenACWY-TT or a quadrivalent polysaccharide vaccine (MenACWY-PS). Here, we report the long-term antibody persistence of the primary dose and the immunogenicity and safety of a booster dose given 10 years after primary vaccination of subjects.

Methods
Participants were enrolled from the Philippines and received a booster dose of MenACWY-TT at 10 years postvaccination. Antibody persistence 10 years postprimary vaccination and immunogenicity 1 month after the booster dose were evaluated by serum bactericidal activity assays using rabbit complement (rSBA) to assess the percentages of subjects with titers ≥ 1:8 and ≥ 1:128 and geometric mean titers (GMTs) for each serogroup. Safety was assessed for the booster dose.

Results
Of 229 subjects enrolled in this extension study, 169 and 58 subjects in the MenACWY-TT and MenACWY-PS groups, respectively, completed the booster phase. The percentages of primary MenACWY-TT recipients with prebooster rSBA titers ≥ 1:8 and ≥ 1:128 at year 10 ranged from 71.6%‒90.7% and 64.8%‒85.2% for all serogroups, respectively, compared with 43.1%‒82.4% and 25.5%‒76.5% of primary MenACWY-PS recipients; rSBA GMTs for all serogroups were higher in the MenACWY-TT group than in the MenACWY-PS group at year 10. For the MenACWY-TT and MenACWY-PS groups, respectively, the MenACWY-TT booster dose elicited rSBA titers ≥ 1:8 in 100% and ≥ 98.0% of subjects (figure); 100% and ≥ 96.1% of all subjects had titers ≥ 1:128. For all serogroups, rSBA GMTs at 1 month after the booster dose were higher than before the booster dose. No new safety signals were observed during the booster phase.

Conclusion
Functional antibody responses elicited by MenACWY-TT persisted 10 years after primary vaccination; the booster dose was well tolerated and elicited robust immune responses.

ClinicalTrials.gov
NCT03189745, EudraCT # 2013-001512-29. Funded by Pfizer.

Disclosures
All authors: No reported disclosures.
2729. mRNA Vaccines Encoding Conserved Influenza Antigens Induce Robust and Durable Immunity in Rhesus Macaques
Authors: Flynn Jessica , Cox Kara , Touch Sinoeun , Ou Yangsi , Weber Teresa , Citron Michael , Bahl Kapil , Ciaramella Giuseppe , Espeseth Amy , Zhang Lan 
Published: October 2019

Abstract

Background
In response to immune pressure, influenza virus evolves, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response that can recognize multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the immunogenicity of mRNA vaccines encoding the stem domain of hemagglutinin (HA) or nucleoprotein (NP) in nonhuman primates (NHPs).

Methods
Rhesus macaques were immunized three times intramuscularly, at 28 day intervals, with lipid nanoparticle-encapsulated mRNA encoding either HA stem (Yassine et al, 2015) or NP. Serum and PBMCs were collected up to 14 or 24 weeks, respectively, after the last vaccination. The magnitude and durability of humoral and cell-mediated immunity were evaluated. ELISA, competition ELISA, an in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter bioassay, and microneutralization assays were used to characterize serum immune responses. Intracellular cytokine staining (IFN-gamma and IL-2) was used to assess antigen-specific T-cell responses.

Results
HA stem-immunized NHPs developed a robust anti-stem binding titer after a single vaccine dose, and after two doses, serum antibodies recognized several antigenically distinct Group 1 HA proteins. This broad antibody response persisted for at least 14 weeks post-dose 3 (PD3). Serum antibodies showed ADCC activity and competed with a well-characterized broadly neutralizing antibody, CR9114, for binding to HA stem; however, the polyclonal serum had only minimal activity against a panel of H1N1 viruses in a microneutralization assay. HA-specific CD4+ T-cell responses were detectable PD3. A robust antibody binding response was also detected in NP-vaccinated NHPs, and titers remained high for at least 14 weeks PD3. Additionally, these animals developed robust NP-specific T-cell responses that persisted for at least 24 weeks PD3. On average, 0.5% of CD4+ and 4% of CD8+ T cells produced IFN-gamma in response to NP peptide stimulation at the peak of the response, 2 weeks after the last vaccine dose was administered.

Conclusion
Lipid nanoparticle-encapsulated mRNA vaccines encoding conserved influenza antigens induce a robust and durable immune response in NHPs.

Disclosures
All authors: No reported disclosures.
2733. Association Between Influenza Vaccination Coverage and Ambulatory Antibiotic Prescription Rates in Children in South Carolina
Authors: Younas Mariam , Royer Julie , Rac Hana , Weissman Sharon , Waites Katie , Bookstaver P Brandon , Justo Julie Ann , Bell Linda J , Al-hasan Majdi 
Published: October 2019

Abstract

Background
Prior studies demonstrated an increase in ambulatory antibiotic prescription rates during the peak of Influenza virus activity, which often occurs during the first 4 months of the year in Southeastern United States. However, the impact of Influenza vaccination coverage on antibiotic prescription rates remains undefined. The purpose of this retrospective cohort study is to examine the association between Influenza vaccination coverage and ambulatory antibiotic prescription rates in children in South Carolina from 2012 to 2017.

Methods
Medicaid and State Employee Health Plan pharmacy claims for outpatient oral antibiotics were utilized for estimation of community antibiotic prescription rates in South Carolina population 6 months to 17 years of age from January 1, 2012 to December 31, 2017, which represents approximately 60% of the South Carolina population in this age group. Linear regression was used to examine the association between antibiotic prescription rates in January to April of each year and Influenza vaccine coverage in children 6 months to 17 years old after adjustments for Influenza vaccine effectiveness in that season as obtained from Centers for Disease Control and Prevention (CDC).

Results
During the 6-year study period, the mean antimicrobial prescription rate in children in South Carolina declined from 103 to 79 per 1000 person-months for the months January through April indicating a 26% decline (P < 0.0001). Influenza vaccine coverage also increased from 50.6% during the first Influenza season of the study and peaked at 60.7% in 2014–2015 Influenza season (Figure 1). After adjusting for the vaccine effectiveness, the decline in antibiotic prescription rate was significantly associated with an increase in vaccine coverage in children (P-value < 0.01). Antibiotic prescription rates declined by 3 per 1,000 person-months for each 1% increase in Influenza vaccine coverage in children.

Conclusion
There is a temporal association between the increase in Influenza vaccination coverage and the decline in ambulatory antibiotic prescription rates in children in South Carolina. Achieving the CDC’s set target Influenza vaccination coverage of 70% of the population may be associated with greater decline in ambulatory antibiotic prescription rates in children in the future.

Disclosures
All authors: No reported disclosures.
2734. Lack of Influence of Early Exposure to Influenza A(H3N2) Viruses on Vaccine Effectiveness Against A(H3N2)-Associated Illness in US Children <18 Years, 2016–2018
Authors: Ladva Chandresh N , Belongia Edward , Monto Arnold , Martin Emily T , Gaglani Manjusha , Reis Michael , Jackson Michael L , Jackson Lisa , Zimmerman Richard , Nowalk Mary Patricia , McLean Huong , Patel Manish , Fry Alicia M , Flannery Brendan 
Published: October 2019

Abstract

Background
During 2017–2018, influenza vaccine effectiveness (VE) against A(H3N2) illness was highest among children <5 years compared with all other ages. A child’s first influenza infection can shape later immune responses. The emergence of antigenically distinct influenza A(H3N2) viruses in 2014–2015 provided an opportunity to explore potential effects of first virus infection on vaccine effects. We compared VE against influenza A(H3N2) during 2016–2017 and 2017–2018 among children born after and before 2014.

Methods
Outpatient children aged 6 months–17 years with acute respiratory illness with cough were enrolled in the United States Influenza VE Network and tested for influenza infection by RT–PCR. Vaccination status was derived through medical records and immunization registries. Children with partial or unknown vaccination status were excluded. We used a test-negative design to estimate VE and 95% confidence intervals (CI) from logistic regression, adjusting for potential confounders. Cohorts were defined by birth after or before June 2014; we assumed exposure to the new A(H3N2) virus among children born after June 2014.

Results
During 2016–2017, among 2,545 children, 445 (18%) tested positive for A(H3N2) and 1,809 (71%) tested negative. VE against A(H3N2) did not differ among children born after June 2014 and among those born before June 2014 [49% (95% CI: −12%, 77%) vs. 43% (27%, 55%); interaction P < 0.75]. During 2017–2018, among 2,936 patients, 631 (22%) tested positive for A(H3N2), and 1,852 (63%) tested negative. VE against A(H3N2) was 59% (36%, 74%) among children born after June 2014 vs. 20% (−1%, 37%) among those born before June 2014 (interaction P < 0.01).

Conclusion
We did not consistently see differences in VE against A(H3N2) between children potentially exposed to different A(H3N2) viruses. However, error in exposure assignment to A(H3N2) viruses and few seasons since the emergence of the new A(H3N2) viruses limit our interpretation. Future study will include additional A(H3N2) seasons as initial exposures to current circulating viruses increase among young children. Alternative explanations for age-related differences will also be explored, such as prior seasonal vaccination.

Disclosures
All authors: No reported disclosures.
2753. Induction of Broadly Cross-Reactive Immune Responses Against A(H3N2) Airuses: Results of a Phase 2 Trial of a Novel Recombinant Hemagglutinin Saponin-Adjuvanted Nanoparticle Seasonal Influenza Vaccine
Authors: Shinde Vivek , Cai Rongman , Plested Joyce S , Zhou Bin , Zhou Haixia , Zhu Mingzhu , Wang Nan , Cloney-Clark Shane , Agrawal Sapeck , Spindler Michelle S , Patel Nita , Massare Michael , Smith Gale , Thomas D Nigel , Cho Iksung , Fries Louis F , Glenn Gregory M 
Published: October 2019

Abstract

Background
We developed a recombinant saponin-adjuvanted (Matrix-M1) quadrivalent hemagglutinin nanoparticle influenza vaccine (qNIV; NanoFlu) for older adults to address two impediments to efficacy of current, predominantly egg-derived, seasonal influenza vaccines: (1) limited protection against antigenic drift variants, particularly H3N2 viruses; and (2) antigenic mismatch between vaccine and circulating strains due to egg-adaptive mutations arising during manufacturing. In a prior Phase 1 trial, we showed that qNIV induced robust, broadly cross-reactive antibody responses against multiple antigenically drifted H3N2 viruses, which were 47–64% better than the egg-derived comparator trivalent high-dose inactivated influenza vaccine (IIV3-HD; Fluzone-High Dose). We undertook a Phase 2 trial to optimize the formulation of qNIV, and to compare qNIV immune responses to those of IIV3-HD and quadrivalent recombinant influenza vaccine (RIV4; FluBlok).

Methods
In this phase 2 dose and formulation finding RCT, we randomized 1,375 subjects aged ≥65 years to be immunized with 1 of 7 test vaccines: 5 different formulations of qNIV, IIV3-HD, or RIV4; and assessed wild-type hemagglutinin-inhibition (wt-HAI) and microneutralization (wt-MN) antibody responses (Day 0/28/56).

Results
Matrix-M1-adjuvanted qNIV induced 15–29% higher wt-HAI titers across 5 vaccine homologous or drifted H3N2 strains at Day 28 relative to unadjuvanted qNIV (statistically significantly superior for 5 of 6 strains tested). At Day 28, several qNIV formulations induced significantly superior wt-HAI titers vs. IIV3-HD (39–45%, 17–22%, and 44–48% greater titers for homologous A/Singapore/INFIMH-16–0019/2016—H3N2, historic-drifted A/Switzerland/9715293/2013—H3N2, and forward-drifted A/Wisconsin/19/2017—H3N2, respectively); and comparable HAI titers vs. RIV4. Wt-MN and wt-HAI data showed concordant patterns across treatment groups.

Conclusion
qNIV induced superior wt-HAI antibody responses vs. IIV3-HD against homologous or drifted H3N2 viruses and similar responses to RIV4. qNIV may address several critical challenges confronting current egg-derived influenza vaccines, especially in the older adult population.

Disclosures
All authors: No reported disclosures.