Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals

Desmond Curran, PhD; Joon H. Kim, MD; Sean Matthews, MSc; Christophe Dessart, MSc; Myron J. Levin, MD; Lidia Oostvogels, MD; Megan E. Riley, PhD; Kenneth E. Schmader, MD; Anthony L. Cunningham, MD; Shelly A. McNeil, MD; Anne E. Schuind, MD; Melissa K. Andrew, MD

Disclosures

J Am Geriatr Soc. 2021;69(3):744-752. 

In This Article

Results

Of the 29,305 participants from the pooled ZOE-50 and ZOE-70 TVC, 26,976 participants (92%) were included in the TVC of ZOE-Frailty (Figure 1, Supplementary Table S4). Participants mean age at baseline was 68.8 years, 58.1% were female and 74.6% were Caucasian (Supplementary Table S5). In the TVC, 42.7% of participants were classified as non-frail, 45.6% as pre-frail and 11.3% as frail (Table 1). The percentage of frail participants increased with age from 5.7% of participants aged 50–59 years to 22.7% of participants aged ≥80 years. A higher proportion of females were frail (12.5%) compared with males (9.5%; P < .001).

Figure 1.

Study population. Abbreviations: HZ, herpes zoster; N, number of participants; QoL, quality of life; TVC, total vaccinated cohort; YOA, years of age.

Vaccine Efficacy

A total of 430 and 31 subjects developed HZ in the Placebo and RZV groups, respectively. VE against HZ was 95.8% in non-frail participants, 90.4% in pre-frail participants and 90.2% in frail participants (Supplementary Table S3). The VE against ZBPI BOI score was 98.6% in non-frail participants, 92.6% in pre-frail participants and 85.2% in frail participants. The absolute reduction in BOI score between the Placebo and RZV groups was higher in frail (2.330–0.345 = 1.985) compared with non-frail (1.173–0.017 = 1.156) participants (Figure 2).

Figure 2.

ZBPI burden of illness by vaccine group and frailty status (modified total vaccinated cohort). Abbreviations: RZV, adjuvanted recombinant zoster vaccine; ZBPI, Zoster Brief PainInventory. [Color figure can be viewed at wileyonlinelibrary.com]

Vaccine Immunogenicity

VRRs for anti-gE antibody were highest at 1 month post-dose two in the RZV group for all frailty subgroups: that is, 98.0%, 97.9%, and 95.7% for non-frail, pre-frail, and frail, respectively (Figure 3). At 36 months post-dose two, the VRR for anti-gE antibody in the RZV group remained high for all frailty subgroups: 81.7%, 74.6%, and 62.0% for non-frail, pre-frail, and frail, respectively. In frail participants, geometric mean anti-gE antibody concentrations increased by approximately 31-fold at 1 month post-dose two and remained 6-fold over baseline in RZV recipients 36 months post-dose two. The corresponding estimates for the non-frail subgroup were 42-fold and 10-fold increases over baseline in RZV recipients at 1 month post-dose two and 36 months post-dose two. In the CMI subset (Supplementary Table S4), VRRs for gE-specific CD42+ T-cells were highest at 1 month post-dose two in the RZV group for all frailty subgroups: 91.7%, 94.2%, and 92.9% in non-frail, pre-frail, and frail participants, respectively. At 36 months post-dose two, the CMI VRR in the RZV group was 58.6%, 48.9%, and 33.3% for non-frail, pre-frail, and frail subgroups, respectively. In frail participants, median CD42+ T-cell frequencies increased by approximately 21-fold (1 month post-dose two) and remained sevenfold (36 months post-dose two) over baseline in RZV recipients. The corresponding estimates for the non-frail subgroup were 22-fold and sevenfold increases over baseline in RZV recipients at 1 month post-dose two and 36 months post-dose two.

Figure 3.

RZV-induced anti-glycoprotein E antibody responses: percentage of responders by frailty status (A), GMCs by frailty status (B); and RZV-induced glycoprotein E-specific cell-mediated immunity: percentage of responders by frailty status (C), CD42+frequencies by frailty status (D). Abbreviations: ELISA, enzyme-linked immunosorbent assay; gE, glycoprotein E; GMC, geometric mean concentration; IU, international units; N, number of participants with available results in each group; Q1/Q3, first and third quartiles; RZV, adjuvanted recombinant zoster vaccine.

Reactogenicity

The percentage of participants reporting any solicited AE was higher in the RZV group than in the placebo group for all frailty subgroups during the 7-day (days 0–6) post-vaccination periods following each dose (Supplementary Table S6). The percentage of participants reporting any solicited AEs decreased with increasing frailty in the RZV group (87.3%, 83.4%, and 73.5% for non-frail, pre-frail, and frail, respectively) and were similar across frailty subgroups in the placebo group (32.2%, 33.7%, and 36.1% for non-frail, pre-frail, and frail, respectively). The percentage of participants reporting any grade 3 solicited AEs were similar across frailty subgroups in the RZV group (17.4%, 14.1%, and 15.3% for non-frail, pre-frail, and frail, respectively) and were higher in the frail than the pre-frail and non-frail subgroups in the placebo group (1.8%, 2.2%, and 5.1% for non-frail, pre-frail, and frail, respectively).

Pain was the most frequently reported solicited local AE for each frailty subgroup in both treatment groups (Table 2). Pain decreased with increasing frailty in the RZV group (82.5%, 75.6%, and 65.8% for non-frail, pre-frail, and frail, respectively) and was similar across frailty subgroups in the placebo group (10.3%, 10.7%, and 10.9% for non-frail, pre-frail, and frail, respectively). Pain was also the most frequently reported grade 3 solicited local AE in each frailty subgroup in both treatment groups. Reporting of grade 3 pain was similar across frailty subgroups in both the RZV and placebo groups.

Fatigue and myalgia were the most frequently reported solicited general AEs for each frailty subgroup in both treatment groups. The percentage of participants reporting fatigue decreased with increasing frailty in the RZV group (47.4%, 43.0%, and 33.6% for non-frail, pre-frail, and frail, respectively) and tended to increase with increasing frailty in the placebo group (14.8%, 17.3%, and 20.5% for non-frail, pre-frail, and frail, respectively). Similarly, the percentage of participants reporting myalgia decreased with increasing frailty in the RZV group (47.4%, 42.0%, and 35.5% for non-frail, pre-frail, and frail, respectively) and tended to increase with increasing frailty in the placebo group (10.3%, 11.5%, and 16.0% for non-frail, pre-frail, and frail, respectively).

Safety

The percentage of participants reporting at least one unsolicited AE within the 30-day post-vaccination (days 0–29) was similar across frailty subgroups in the RZV group (51.6%, 49.7%, and 47.9% for non-frail, pre-frail, and frail, respectively), and tended to increase with increasing frailty in the placebo group (29.6%, 32.7%, and 35.5% for non-frail, pre-frail, and frail, respectively (Supplementary Figure S1). The percentage of participants experiencing at least one pIMD was 1.3%, 1.3%, and 1.0% in the non-frail, pre-frail, and frail subgroups of the RZV group, respectively. This was similar to the percentages observed in the placebo group (1.2%, 1.4%, and 1.8% in the non-frail, pre-frail, and frail subgroups, respectively). The percentage of participants experiencing at least one SAE was 6.2%, 11.5%, and 18.6% in the non-frail, pre-frail, and frail subgroups of the RZV group, respectively, and 5.7%, 12.1%, and 22.7% in the non-frail, pre-frail, and frail subgroups of the placebo group, respectively. The percentage of participants who died during the study follow-up (and who were classified per protocol as experiencing a fatal SAE, independent of relationship to vaccination) was 2.1%, 4.9%, and 11.1% in the non-frail, pre-frail, and frail subgroups of the RZV group, respectively, and 1.9%, 5.5%, and 12.4% in the non-frail, pre-frail, and frail subgroups of the placebo group, respectively.

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