05. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Updates from Year 3 of Multi-Site Trial

Abstract Background The SARS-CoV-2 pandemic has spotlighted respiratory infections and the value of effective vaccines. The SARS-CoV-2 vaccine has been remarkably effective; however, influenza vaccine effectiveness has been reported to be lower among active duty military populations than in the general public (18% vs 36%). The Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study compares 3 FDA-licensed influenza vaccine types (egg-based, cell-based, and recombinant) to assess differences in immunogenicity and effectiveness in adults. Methods Participants in the 3rd year of PAIVED (2020/21 influenza season) were enrolled from October 2020 through January 2021. Participants received weekly surveys about influenza-like-illnesses (ILI) experienced in the past week; if they reported an ILI, they were queried about symptom duration and severity, and asked to self-collect a nasal swab and dried blood sample. Four weeks later, more information about symptom duration and illness burden was obtained via telephone interview, and the participant collected a second blood sample. Results PAIVED year 3 enrolled 3,269 participants (Table 1). 278 participants reported 1 ILI , while 60 reported 2 ILIs, and 18 reported 3 ILIs. No pathogen was identified for most processed ILI samples (78%); the most common viruses were SARS-CoV-2 (25, 12%), rhinovirus (24, 12%), and seasonal coronaviruses (4, 2%). No influenza has been identified thus far. Among those participants who had convalescent ILI visits (275), the median duration of the reported ILIs was 9 days (IQR 5, 15), with a median of 4 days (IQR 2, 7) of limited activity, and 2 days (IQR 0, 3) with fever. Three individuals were hospitalized. Conclusion There have been relatively low rates of ILI identified in this study during this season, with only 11% of the participants reporting an ILI so far, consistent with low rates of non-COVID-19 ILI reported elsewhere during the current pandemic. We anticipate some influenza cases may be identified as more samples are processed. Planned analyses include calculating comparative influenza vaccine effectiveness to inform future vaccine purchasing decisions, as well as comparing serological response to the different vaccines. Disclosures Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Jitu Modi, MD, GSK (Speaker’s Bureau)

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1501. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Updates from Year 2 of multi-site trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1682 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S752-S753

Author(s):

Stephanie A Richard ◽

Timothy Burgess ◽

Limone Collins ◽

Rhonda Colombo ◽

...

Keyword(s):

Influenza Vaccine ◽

Clinic Visit ◽

Vaccine Effectiveness ◽

Symptom Duration ◽

Blood Draw ◽

Duration Of Symptoms ◽

Nasal Swabs ◽

Second Year ◽

Military Facilities ◽

Pragmatic Assessment

Abstract Background Despite nearly universal influenza vaccination for active duty military personnel, breakthrough influenza infections occur. We are reporting on the second year of the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED), comparing three FDA-licensed influenza vaccine types (egg-based, cell -based, and recombinant) to assess differences in immunogenicity and effectiveness. Methods Participants in the second year of PAIVED were enrolled from Oct 2019 through Jan 2020 at 9 military facilities. Participants received weekly inquiries about influenza-like-illnesses (ILI) experienced in the past week, and if the participant reported having a cough or sore throat and a) muscle/body aches or fatigue and/or b) being feverish or having chills, they were scheduled for a clinic visit. During this visit, a blood sample and a nasal swab were collected, as well as information about symptom duration and severity. A second (convalescent) visit was conducted approximately 4 weeks later, which involved collecting additional information about the duration of symptoms and illness burden, as well as a second blood draw. Due to the COVID-19 pandemic, acute and convalescent visits were disrupted at most sites in March and April due to COVID-19 precautions. Results PAIVED year 2 enrolled 5,892 participants who completed demographic forms (Table 1). Among those who reported any ILIs, most reported one ILI (1,345), while 264 reported two ILIs, and 42 reported three ILIs. Nasal swabs were processed from 273 ILIs at four sites (Fig 1), and 14 cases of influenza were identified thus far. The median duration of ILIs was ten days, with a median of three days of limited activity, and two days with fever. Nine individuals were hospitalized. Table 1. Demographic characteristics of individuals enrolled in PAIVED 2019/20 Figure 1. Lab results as of 5/15 (N=273 samples) Conclusion Over 25% of participants reported an ILI, and 5% of the nasal swabs that have been tested thus far have been positive for influenza. While most samples have not yet been analyzed, we have identified some breakthrough cases of influenza among vaccinated participants. Planned analyses include comparative vaccine effectiveness in order to inform future vaccine purchasing decisions. Disclaimer Disclosures All Authors: No reported disclosures

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1338. Before and After: The Impact of the COVID-19 Pandemic on Influenza-Like Illness Trends in PAIVED

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1530 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S756-S757

Author(s):

Rhonda E Colombo ◽

Stephanie A Richard ◽

Christina Schofield ◽

Limone Collins ◽

Anuradha Ganesan ◽

...

Keyword(s):

Influenza Vaccine ◽

Pathogen Detection ◽

Demographic Data ◽

Panel Member ◽

Vaccine Effectiveness ◽

Mitigation Measures ◽

Influenza Surveillance ◽

Review Panel ◽

Influenza Like Illness ◽

The Impact

Abstract Background The Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) is a multicenter study assessing influenza vaccine effectiveness in active duty service members, retirees, and dependents. PAIVED recently completed its third year and offers a unique opportunity to examine influenza-like illness (ILI) trends prior to and during the COVID-19 pandemic in a prospective, well-defined cohort. Methods During the 2018-19, 2019-20, and 2020-21 influenza seasons, PAIVED enrolled DoD beneficiaries presenting for annual influenza vaccination. After collecting baseline demographic data, participants were randomized to receive egg-based, cell-based, or recombinant-derived influenza vaccine. Weekly throughout the influenza season of enrollment, participants were surveyed electronically for ILI, defined as (1) having cough or sore throat, plus (2) feeling feverish/having chills or having body aches/fatigue. Participants with ILI completed a daily symptom diary for seven days and submitted a nasal swab for pathogen detection. Results Over the three seasons, there were 10,656 PAIVED participants: 1514 (14.2%) in 2018-19, 5876 (55.1%) in 2019-20, and 3266 (30.6%) in 2020-21. The majority were male (68-73% per year) with a mean age of 34±14.8 years at enrollment. 2266 participants reported a total of 2673 unique ILIs. The highest percentage of participants with ILI was in 2019-20 (28.2%), versus 19.6% in 2018-19 and 9.6% in 2020-21. Figure 1 depicts the percent of individuals reporting ILI by week of the season for each of the PAIVED seasons. Notably, after March 21, 2020, the weekly incidence of participants reporting ILI never exceeded 1%. Figure 1. Percent of PAIVED participants reporting ILI by week of season. Conclusion The low incidence of reported ILI in PAIVED participants during the COVID-19 pandemic is consistent with national influenza surveillance reports of influenza and outpatient ILI activity, suggesting that mitigation measures taken to reduce transmission of SARS-CoV-2 reduced the spread of other respiratory viruses. Disclaimer Disclosures Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Jitu Modi, MD, GSK (Speaker’s Bureau)

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1178. Sustained Vaccine Effectiveness Against Influenza-Associated Hospitalization in Children: Evidence from the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1371 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S681-S682

Author(s):

Leila C Sahni ◽

Eric A Naioti ◽

Samantha M Olson ◽

Angela P Campbell ◽

Marian G Michaels ◽

...

Keyword(s):

Influenza Vaccine ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Onset Date ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Adult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. Methods We conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models. Results Of 8,430 hospitalized children (4,781 [57%] male; median age 2.4 years), 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases (n=1,000; 12%) were less likely to be vaccinated than influenza-negative controls (39% vs. 61%, p< 0.001) and overall VE against hospitalization was 53% (95% CI: 46%, 60%). Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96% (95% CI: -0.76%, 2.71%) per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66% (95% CI: -0.76%, 2.71%) per week in children ≤ 8 years (n=3,084) and 2.16% (95% CI: -1.68%, 6.15%) per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage. Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group (b: ≤ 8 years; c: 9-17 years) Conclusion We observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Disclosures Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

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2756. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED), Influenza-Like-Illnesses (ILIs) Sub-Study at the Marine Corps Recruit Depot-San Diego, CA (MCRD-SD) During the 2018–2019 Influenza Season

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2433 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S970-S971

Author(s):

Ryan Maves ◽

Gregory Utz ◽

Stephanie Richard ◽

Melissa Smith ◽

Limone Collins ◽

...

Keyword(s):

Influenza Vaccine ◽

San Diego ◽

Diagnostic Testing ◽

Prospective Trial ◽

Marine Corps ◽

Vaccine Effectiveness ◽

Training Time ◽

Military Recruits ◽

Nasal Swabs ◽

Pragmatic Assessment

Abstract Background Military recruits suffer high rates of influenza and influenza-like illness (ILI) during training. ILIs may lead to morbidity, lost training time, and hospitalization. We evaluated the incidence and clinical outcomes of ILI among recruits at Marine Corps Recruit Depot San Diego (MCRD-SD) in a prospective trial of influenza vaccine efficacy. Methods Recruits at MCRD-SD were enrolled to compare the effectiveness of 3 types of FDA approved influenza vaccine: Afluria®, an egg-based vaccine; Flucelvax®, a cell-culture-derived vaccine; and Flublok®, a recombinant vaccine. Four companies of recruits were enrolled sequentially from 28 November 2018 to 19 December 2018, then randomized in a 1:1:1 ratio. Participants were followed for 18 weeks at MCRD-SD and Camp Pendleton. All participants who presented with ILI symptoms at medical care sites underwent viral diagnostic testing in addition to immunologic studies. Recruits were excluded from participation if <18 years of age, if previously vaccinated in the 2018–2019 season, or if reporting allergy to the vaccines. Results Of 1338 recruits approached, 771 (57.6%) participants consented for enrollment. All recruits were men between 18 and 28 years. There were 182 ILIs amongst 177 recruits (23% of 771 recruits). Nasal swabs were obtained in 180/182 cases (99%). Mean duration of ILI symptoms was 7 days. Mean days of fever was 4. Subjects reported a total 168 days of reduced training (range 0–14 days; mean 0.9 days). There were 47 total days of missed training for all subjects (range of 0–4 days; mean 0.3 days/subject). There were no hospitalizations related to ILIs. Approximately 82% (148/182) of ILIs presented within the first 3 weeks of training; 44% (80/182) of ILIs occurred during the second week of training. PCR- nasal swabs results; race/ethnicity data, and frequency of ILI mapped to week of training are illustrated below. Conclusion ILIs can negatively impact training effectiveness. Days lost to training from ILIs and hospitalizations can prevent successful completion of training with impact on military readiness. PAIVED may inform the DoD on future strategies to minimize influenza and other respiratory threats in recruit military populations. Influenza vaccine effectiveness will be reported separately. Disclosures All authors: No reported disclosures.

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1373. Vaccine Effectiveness and Pneumococcal Serotypes in Pediatric Otitis Media in the Era of Routine 13-valent Pneumococcal Vaccination in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1555 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S696-S697

Author(s):

Kristina G Hulten ◽

William Barson ◽

P Ling Lin ◽

John S Bradley ◽

Timothy R Peters ◽

...

Keyword(s):

Otitis Media ◽

Acute Otitis Media ◽

Pneumococcal Vaccination ◽

Panel Member ◽

The United States ◽

Vaccine Effectiveness ◽

Pneumococcal Serotypes ◽

Research Support ◽

Review Panel ◽

Research Grant

Abstract Background Pneumococcal acute otitis media (AOM) in children due to vaccine related serotypes (St) declined after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods Patients < 18 years with pneumococcal OM isolates from 2014-2019 from the U S Pediatric Multicenter Pneumococcal Surveillance Group were analyzed for demographics, immunization status, antimicrobial susceptibility and St distribution. p< 0.05 was considered statistically significant. Vaccine effectiveness (VE) was calculated using a standard formula: 1-([PCV13St vaccinated (≥3 PCV13 doses) x Non-PCV13St unvaccinated (0-1 PCV13 doses)]/[PCV13St unvaccinated x Non-PCV13St vaccinated]) Results 646 patients were identified. Patients with PCV13 St were older compared to patients with non-PCV13 serotypes (3.3 vs 1.5 median years, p< 0.0001). Most isolates were from spontaneous drainage (71.4 %) and PE tube placements (26.9%). 36 different Sts were identified; 83.4% of isolates were non-PCV13 Sts; 35B represented 18.3% of all isolates. St 19A decreased over time (p=0.0003). 14% of isolates had penicillin MIC ≥2 µg/ml and 2.4% had ceftriaxone MIC >1 µg/ml. (Figure) 633 patients had known vaccine status. VE was 86.4% (Table). Table. Conclusion Non-PCV13 Sts caused most pneumococcal OM. St35B was the most common St. St 19A decreased as a cause of otitis. In this study the VE of≥3 PCV13 doses was 86% for pneumococcal OM. Disclosures Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support)

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2757. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Immunogenicity Sub-Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2434 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S971-S972

Author(s):

Rhonda Colombo ◽

Stephanie Richard ◽

Christina Schofield ◽

Limone Collins ◽

Anuradha Ganesan ◽

...

Keyword(s):

Influenza Vaccine ◽

Vaccine Effectiveness ◽

Vaccine Uptake ◽

Buccal Swab ◽

Study Cohort ◽

Blood Draw ◽

Physically Active ◽

Vaccine Type ◽

Study Participants ◽

Pragmatic Assessment

Abstract Background Despite greater than 90% of US active duty (AD) military personnel receiving influenza vaccination annually, vaccine effectiveness (VE) among AD members has been substantially lower than in groups with less vaccine uptake. The substrate used in vaccine production may impact immunogenicity and thus VE. The PAIVED study is investigating VE of 3 different influenza vaccine formulations; a sub-study assesses immunogenicity. This analysis compares demographic characteristics and influenza-like illness (ILI) experience among main and sub-study participants for the first year of PAIVED. Methods During the 2018–2019 influenza season, PAIVED enrolled participants at 5 military medical centers, recruiting sub-study subjects from the main cohort excluding marine recruits. All participants were randomized (1:1:1) to receive either egg-based, cell-culture based or recombinant influenza vaccine. At enrollment, participants provided key demographic and behavioral data. Weekly surveillance for ILI symptoms was performed electronically. Sub-study volunteers underwent an additional blood draw prior to and at 21–35 days post vaccination ± an optional buccal swab. Results 200 (23.5%) of 852 non-recruit PAIVED participants enrolled in the immunogenicity sub-study. Similar to the main cohort, 46% of sub-study volunteers were female, 85% were physically active, and 6% smoked tobacco. Sub-study participants were younger (47 ± 16 years vs. 51 ± 17 years, P = 0.004) and more likely to be AD (34% vs. 22%, P = 0.001). Although 70% of both groups identified as White, the percent African American (20% sub-study; 13% main), Asian (3%; 7%), multi-racial (2%; 5%), and unknown (6%; 4%) differed (P = 0.02). More sub-study participants developed an ILI (19% vs. 12%, P = 0.02). Conclusion The convenience sampling method used for recruitment into the sub-study was effective. The younger age and higher AD status in the sub-study group may be informative for evaluation of military readiness issues. The greater incidence of ILI in the sub-study increases the chance differences in immune response by vaccine type may be interpretable in the context of circulating influenza strains. Targeted efforts to enhance recruitment of a racially diverse sub-study cohort may be warranted. Disclosures All authors: No reported disclosures.

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