A randomized trial assessing the efficacy, immunogenicity, and safety of vaccination with live attenuated varicella zoster virus-containing vaccines: ten-year follow-up in Russian children

Figures & data

Figure 1. Plain language summary to summarize the findings and highlight their clinical relevance.

Figure 2. Study design.

N, number of participants; AEs, adverse events; MMR, combined trivalent measles, mumps, and rubella vaccine; MMRV, combined tetravalent measles, mumps, rubella, and varicella vaccine; V, monovalent varicella vaccine; V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of the tetravalent measles, mumps, rubella, and varicella vaccine.* only applicable to the subset for MMR testing.

Figure 3. Participant flow chart.

ATP, according-to-protocol; N, number of participants; MMR, measles, mumps, and rubella; V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of the tetravalent measles, mumps, rubella, and varicella vaccine.

Table 1. Demographic characteristics of the study participants (total vaccinated cohort)

	V2 group N = 426	V1 group N = 431	V0 group* N = 143
Age in months, mean (± SD)	12.7 (1.7)	12.6 (1.4)	12.6 (1.2)
Female sex, n (%)	198 (46.5)	210 (48.7)	69 (48.3)
Race, n (%)
ߓWhite/Caucasian	423 (99.3)	428 (99.3)	143 (100)
ߓArabic/North African	1 (0.2)	0 (0.0)	0 (0.0)
ߓEast/South East Asian	2 (0.5)	2 (0.5)	0 (0.0)
ߓSouth Asian	0 (0.0)	1 (0.2)	0 (0.0)
Contact with other children, n (%)
ߓAt least one sibling at home	94 (22.1)	98 (22.7)	32 (22.4)
ߓAttending a day care center	368 (86.4)	376 (87.2)	125 (87.4)
ߓAttending a childminder	22 (5.2)	23 (5.3)	12 (8.4)
ߓAt least once a week at other places	392 (92.0)	399 (92.6)	131 (91.6)

N, total number of participants; n (%), number (percentage) of participants in a given category; SD, standard deviation; V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of tetravalent measles, mumps, rubella, and varicella vaccine.

* data for the V0 group (control group) were also published in Gillard 2021.⁴⁵

Table 2. Vaccine efficacy estimates against confirmed varicella cases (according-to-protocol cohort for efficacy)

	n/N	Total time to event (years)	Incidence rate (95% CI) per 100 person-years	Vaccine efficacy (95% CI)
V2 group	7/378	1480	0.5 (0.2–1.0)	92.4% (82.3–96.7)
V1 group	24/392	1471	1.6 (1.1–2.4)	74.7% (55.5–85.6)
V0 group	25/130	377	6.6* (4.5–9.8)	–

N, total number of participants; n, number of participants reporting at least one event; CI, confidence interval; V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of tetravalent measles, mumps, rubella, and varicella vaccine.

* data for the V0 group (control group) were also published in Gillard 2021.⁴⁵

Figure 4. Anti-varicella zoster virus (VZV) antibody persistence during ten years of follow-up (adapted according-to-protocol cohort for persistence).

GMC, geometric mean concentration; n (%), number (percentage) of participants with anti-varicella zoster virus antibody geometric mean concentration equal to or above the limit of detection (25 mIU/mL); V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of the tetravalent measles, mumps, rubella, and varicella vaccine. The error bars represent the 95% confidence interval.

Figure 5. Anti-measles (A), -mumps (B), and -rubella (C) antibody persistence during two years of follow-up (adapted according-to-protocol cohort for persistence, subset for MMR testing).

GMC, geometric mean concentration; n (%), number (percentage) of participants with antibody GMC equal to or above the seropositivity threshold (150 mIU/mL for anti-measles, 231 U/mL for anti-mumps, and 4 IU/mL for anti-rubella antibodies); MMR, measles, mumps, and rubella; V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of the tetravalent measles, mumps, rubella, and varicella vaccine. The error bars represent the 95% confidence interval.

Figure 6. Incidence of solicited local adverse events (pain, redness, and swelling) from day 0 to day 3, and solicited general symptoms (fever and rash) from day 0 to day 42, after each dose (total vaccinated cohort, subset for MMR testing).

MMR, measles, mumps, and rubella; V0 group, control group receiving two doses of trivalent measles, mumps, and rubella vaccine (no varicella vaccine); V1 group, group receiving one dose of trivalent measles, mumps, and rubella vaccine followed by one dose of monovalent varicella vaccine; V2 group, group receiving two doses of the tetravalent measles, mumps, rubella, and varicella vaccine. The error bars represent the 95% confidence interval. See supplementary methods for definition of grade 3 intensity.

Table

AE	adverse event
ATP	according-to-protocol
CI	confidence interval
ELISA	enzyme-linked immunosorbent assay
GMC	geometric mean concentration
HR	hazard ratio
HZ	herpes zoster
IDMC	independent data monitoring committee
IgG	immunoglobulin G
IU	international units
LAR	legally acceptable representative
MMR	measles mumps and rubella
MMRV	measles mumps rubella and varicella
PCR	polymerase chain reaction
SAE	serious adverse event
SAS	Statistical Analysis System
TVC	total vaccinated cohort
USA	United States of America
UVV	universal varicella vaccination
monovalent V vaccine	monovalent varicella vaccine
V0	group of children receiving two doses of the combined trivalent measles mumps and rubella vaccine
V1	group of children receiving one dose of the combined trivalent measles mumps and rubella vaccine followed by one dose of varicella vaccine
V2	group of children receiving two doses of the combined tetravalent measles mumps rubella and varicella vaccine
VCV	varicella zoster virus-containing vaccine
VE	vaccine efficacy
VZV	varicella zoster virus
WHO	World Health Organization

Gillard P, Povey M, Carryn S. Clinically- versus serologically-identified varicella: a hidden infection burden. A ten-year follow-up from a randomized study in varicella-endemic countries. Hum Vaccin Immunother. 2021:1–10. doi:10.1080/21645515.2021.1932217.

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