08. Concomitant Administration of the Adjuvanted Recombinant Zoster Vaccine (RZV) with 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Is Safe and Does Not Interfere with Immunogenicity of Either Vaccine in Adults Aged ≥ 50 Years

Abstract Background This study assessed non-inferiority of humoral immunogenicity, reactogenicity, and safety of RZV when the 1st dose was co-administered with PCV13 in adults ≥ 50 years of age (YOA) compared to sequential administration. Methods In this phase 3b, open-label, multi-center study (NCT03439657), adults were randomized 1:1 to receive either the 1st RZV dose co-administered with PCV13 at day (D)1 and the 2nd RZV dose at month (M)2 (Co-Ad group), or PCV13 at D1, the 1st RZV dose at M2 and the 2nd RZV dose at M4 (Control group). Co-primary confirmatory objectives were: (i) vaccine response rate (VRR) to RZV at 1 month post-dose 2 in Co-Ad group; (ii) non-inferiority of humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group compared to Control group. Solicited adverse events (AEs) until D7 post-vaccination and unsolicited AEs until D30 post-vaccination were recorded. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected through 12 months post-RZV dose 2. Immunogenicity was performed in the per-protocol set (PPS) and safety analyses in the exposed set. Results Of 912 vaccinated adults, 863 were included in PPS (Co-Ad: 427; Control: 436). VRR for anti-glycoprotein E antibody concentrations was 99.1% in Co-Ad group. The predefined non-inferiority criteria for the humoral immune responses to RZV and PCV13 were met (Table 1). The overall frequency of solicited local AEs after RZV and PCV13 was comparable between Co-Ad and Control groups. Pain was the most common solicited local AE (Figure 1). The frequency of solicited general AEs was similar for the 1st RZV dose when co-administered with PCV13 or alone (57.4% vs 54.6%). Myalgia and fatigue were the most common solicited general AEs (Figure 2). The frequency (Co-Ad: 21.2%; Control: 23.1%) and nature of unsolicited AEs were balanced between groups. None of the reported SAEs, fatal SAEs, or pIMDs were vaccine-related. Table 1. Co-primary confirmatory objectives: vaccine response rate (VRR), and non-inferiority of the immune responses to RZV (1 month post-dose 2) and to PCV13 (1 month post-vaccination) in the Co-Ad group vs the Control group (per-protocol set) Figure 1. The incidence of solicited local adverse events (AEs) occurring within 7 days post-vaccination (overall/adult, exposed set) Figure 2. The incidence of solicited general adverse events (AEs) post-dose 1 occurring within 7 days post-vaccination (exposed set) Conclusion Co-administration of the 1st RZV dose with PCV13 showed non-inferior immune responses to sequential administration. The reactogenicity and safety of RZV in the Co-Ad group were within the range of the established safety profile of RZV. Co-administration of RZV with PCV13 may improve vaccination rates in ≥ 50 YOA population. Funding GlaxoSmithKline Biologicals SA Disclosures Ji-Young Min, PhD, GSK group of companies (Employee) Agnes Mwakingwe-Omar, MD, PhD, GSK group of companies (Employee) Megan Riley, PhD, GSK group of companies (Employee, Shareholder) Lifeter Yenwo Molo, BsC(hons) MSc(hons), GSK group of companies (Employee) Jyoti Soni, MA, GSK group of companies (Employee) Ginette Girard, MD, Diex Recherche Inc. Sherbrooke (Scientific Research Study Investigator) Jasur Danier, MD, GSK group of companies (Employee, Shareholder)

Background. In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV, Shingrix) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥50 years, with the 2 nd dose recommended 2-6 months after the 1 st dose. Among Medicare beneficiaries, 2-dose series completion 6 months and 12 months post initiation was 78% and 86%, respectively. Here we estimate the proportion of adults age 50-64 years who completed the 2-dose RZV series within 6 or 12 months after receiving their 1 st dose, by using two administrative claims databases.

Methods.
We used medical and pharmaceutical claims data from October 2017-March 2020 IQVIA® PharMetrics Plus and October 2017-October 2020 IBM® MarketScan® databases. RZV vaccination was defined using Current Procedural Terminology and National Drug Codes. We allowed for sufficient follow-up time by examining 1 st doses given at least 6 or 12 months prior to the end of the study period in both databases. Place of administration was available in IQVIA data.
Results. Among persons age 50-64 years, in IQVIA and MarketScan, 70% and 68% received their 2 nd RZV dose within 6 months, respectively, and 79% and 81% received their 2 nd dose within 12 months, respectively. The median age of 1 st dose of RZV vaccination was 60 years and ~60% were female [ Table 1]. When the 2 nd dose was administered within 12 months, the median interval between 1 st and 2 nd doses was 104 and 98 days in the IQVIA and MarketScan databases, respectively. Characteristics by age, sex, or region were similar in persons who received 1 RZV dose vs. 2 RZV doses [ Table 1]. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 55% of vaccinations occurred at ambulatory medical provider offices and 40% at pharmacies; among 2 doses recipients, 33% of vaccinations occurred at provider offices and 62% at pharmacies.
Conclusion. Among 50-64-year-olds, 2-dose RZV series completion was ~70% within 6 months and 80% within 12 months of initiation. The findings were similar across two administrative claims databases. Availability of RZV at pharmacies has potentially helped to increase RZV 2 nd dose completion rates. Background. This study assessed non-inferiority of humoral immunogenicity, reactogenicity, and safety of RZV when the 1st dose was co-administered with PCV13 in adults ≥ 50 years of age (YOA) compared to sequential administration.

Concomitant Administration of the Adjuvanted Recombinant Zoster Vaccine ( RZV) with 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Is Safe and Does Not Interfere with Immunogenicity of Either Vaccine in Adults Aged
Methods. In this phase 3b, open-label, multi-center study (NCT03439657), adults were randomized 1:1 to receive either the 1st RZV dose co-administered with PCV13 at day (D)1 and the 2nd RZV dose at month (M)2 (Co-Ad group), or PCV13 at D1, the 1st RZV dose at M2 and the 2nd RZV dose at M4 (Control group). Co-primary confirmatory objectives were: (i) vaccine response rate (VRR) to RZV at 1 month post-dose 2 in Co-Ad group; (ii) non-inferiority of Table 1. Co-primary confirmatory objectives: vaccine response rate (VRR), and non-inferiority of the immune responses to RZV (1 month post-dose 2) and to PCV13 (1 month post-vaccination) in the Co-Ad group vs the Control group (per-protocol set) Figure 1. The incidence of solicited local adverse events (AEs) occurring within 7 days post-vaccination (overall/adult, exposed set) Figure 2. The incidence of solicited general adverse events (AEs) post-dose 1 occurring within 7 days post-vaccination (exposed set)

Conclusion.
Co-administration of the 1st RZV dose with PCV13 showed non-inferior immune responses to sequential administration. The reactogenicity and safety of RZV in the Co-Ad group were within the range of the established safety profile of RZV. Co-administration of RZV with PCV13 may improve vaccination rates in ≥ 50 YOA population. Methods. Ferrets pre-infected with influenza H1N1 and B/Yamagata viruses, were immunized intranasally (IN) with PBS (Mock) or Quad M2SR, or intramuscularly with Fluzone QIV. Serum collected post-vaccination was evaluated for Ab responses. Forty-two days after vaccination, ferrets were challenged IN with 10 6 pfu of B/Brisbane/60/2008 (Victoria lineage) influenza virus. Nasal washes were taken for 7 days post-challenge and evaluated for challenge virus by TCID 50 assay. Nasal turbinates, trachea and lungs were also evaluated for virus.
Results. Quad M2SR and QIV elicited high serum Abs against the vaccine strain B/Colorado/06/2017 (Fig. 1A) and against the drifted influenza B challenge strain B/Brisbane/60/2008 (Fig. 1B) in ferrets with preexisting immunity. Like Mock, ferrets who received QIV displayed both weight loss (6.2%, Fig. 2A) and a rise in temperature (1.1 o C, Fig. 2B) after challenge. In contrast, the Quad M2SR group did not exhibit any significant weight or temperature changes after challenge. Quad M2SR controlled the drifted challenge virus better than QIV as evidenced by significantly lower or absent post-challenge virus titer in nasal washes (Fig. 3A) and nasal turbinates (Fig. 3B).