NA NA

Prevention through vaccination: Immunocompromised patients

Efficacy, immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) in immunocompromised subjects

Patients with immunocompromising conditions are at higher risk for herpes zoster than age-matched immunocompetent controls

This graph summarises the incidence rates of herpes zoster reported in the literature for adults with different conditions. Patients with immunocompromising conditions are at higher risk for herpes zoster than aged-matched immunocompetent controls. For example, patients undergoing stem cell transplantation, who represent the most severely immunocompromised population, have the highest incidence rate of herpes zoster.1-17

incidence-rates-per-1000-person-years-of-herpes-zoster-in-adults-with-immunocompromising-conditions.-incidence-was-estimated-as-between-42.4-and-95.6-per-1000-person-years-in-adults-with-bone-marrow-or-stem-cell-transplant,-between-31.4-and-66.2-in-those-with-haematological-malignancies,-between-31.6-and-40.0-in-those-with-a-heart-transplant-and-between-24.4-and-28.0-in-those-with-renal-transplants.-incidence-of-herpes-zoster-was-18.3-in-adults-who-received-liver-transplants,-between-9.3-and-17.4-in-those-infected-with-h-i-v,-between-6.4-and-32.5-in-those-with-systemic-lupus-erythematosus,-between-12.1-and-12.2-in-those-with-rheumatoid-arthritis,-between-7.6-and-9.3-in-those-with-inflammatory-bowel-disease,-8.6-in-those-with-multiple-sclerosis-and-8.0-in-those-with-psoriasis.-in-immunocompetent-people-of-all-ages,-the-incidence-rate-of-herpes-zoster-per-1000-person-years-was-4.5-

HIV, human immunodeficiency virus.

Overview of the clinical programme for RZV in immunocompromised populations

In the below overview of five clinical trials in different immunocompromised populations, four of which were receiving multiple, concomitant immunosuppressive medications, RZV induced a robust and persistent humoral and cell-mediated immune response (CMI).18

  Human Immunodeficiency Virus (HIV)
People living withHIV19		 Autologous Haematopoietic Stem Cell Transplant (auHSCT) Post-autologous5 Haematological Malignancies
While on immunosuppressive chemotherapy7		 Renal Transplants
Post-renal transplant20		 Solid Tumour
Solid tumour malignancies while on immunosuppressive chemotherapy21
Trial NCT01165203* NCT01610414† NCT01767467 NCT02058589 NCT01798056
Phases Phase 1/2a
(N=123)		 Phase 3
(N=1846)		 Phase 3
(N=562)		 Phase 3
(N=264)		 Phase 3
(N=232)
Trial type Placebo-controlled, ≥18 years of age
Primary
endpoints		 Reactogenicity/
Immunogenicity/
Safety		 Efficacy Reactogenicity/
Immunogenicity/
Efficacy§		 Immunogenicity/
Safety		 Reactogenicity/
Immunogenicity/
Safety
Dose
timeline		 Month 0, 2, 6
(3 doses)		 Month 0, 1–2
  Click here for further information on NCT01165203 Click here for further information on NCT01610414 Click here for further information on NCT01767467 Click here for further information on NCT02058589 Click here for further information on NCT01798056

*RZV was studied in a Phase 1/2a trial in HIV patients; †A phase 1/2, randomised, observer-blind, placebo-controlled study was previously conducted to assess safety and immunogenicity of two formulations of RZV in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukaemia who had undergone autologous haematopoietic stem cell transplantation 50 to 70 days earlier; §Efficacy was evaluated in a post hoc analysis.7

auHSCT, autologous haematopoietic stem cell transplant; HIV, human immunodeficiency virus; RZV, recombinant zoster vaccine.

NA NA

Autologous haematopoietic stem cell transplant (auHSCT)

Post-autologous transplant5

A Phase 3, randomised, observer-blind, placebo-controlled, multicentre clinical trial to assess the prophylactic efficacy, safety and immunogenicity of GSK’s adjuvanted RZV, when administered intramuscularly on a two-dose schedule to adult auHSCT recipients.5,22–24

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†Visit 3: approximately 1 month after the second vaccination.
*Second dose was administered 1 to 2 months after the first dose.
Blood sampling collected from all subjects at Visit 1 and Visit 3. Additional blood samples collected from sub-cohorts at all study visits.

auHSCT, autologous haematopoietic stem cell transplant; RZV, recombinant zoster vaccine; TVC, total vaccinated cohort; YOA, years of age.

Vaccine efficacy against herpes zoster (HZ) and other HZ-related endpoints by age group5,22

 

RZV

N (n)

Placebo

N (n)

 

VE

 

  
% LL UL
VE by Age          
18–49 213 (9) 212 (29) 71.8 38.8 88.3
≥50 657 (40) 639 (106) 67.3 52.6 77.9
Other HZ-related endpoints  
PHN

 870 (1) 851 (9) 89.3 22.5 99.8
HZ-related hospitalisations 870 (2) 851 (13) 84.7 32.1 96.6
Other HZ complications* 870 (3) 851 (13) 77.8 19.0 95.9

*Excluding PHN: disseminated zoster: 3 (recombinant zoster vaccine group) and 13 (placebo group); meningoencephalitis: 1 (placebo group); whole study period, median follow-up time approximately 21 months.

HZ, herpes zoster; LL, lower limit; N, number of subjects included in each group; n, number of subjects having at least one confirmed HZ episode; PHN, post-herpetic neuralgia; RZV, recombinant zoster vaccine; UL, upper limit; VE, vaccine efficacy.

In study participants who completed the two-dose course, the vaccine efficacy in preventing herpes zoster was estimated to be 68.2%.5,22

column-graph-showing-anti–glycoprotein-e-geometric-mean-concentrations-in-autologous-haematopoietic-stem-cell transplantation-patients-prior-to-and-after-vaccination-with-either-the-recombinant-zoster-vaccine-or-placebo.-highest-anti–glycoprotein-e-geometric-mean-concentrations-were-recorded-one-month-after-dose-two,-which-remained-above-baseline-24-months-after-completion-of-the-vaccination-schedule-

gE, glycoprotein E; GMC, geometric mean concentration; Mo, month; RZV, recombinant zoster vaccine.
Graph based on raw data from the Clinical Trial NCT01610414.23

column-graph-showing-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-in-autologous-haematopoietic-stem-cell-transplantation-patients-before-and-after-vaccination-with-the-recombinant-zoster-vaccine-or-placebo.-the-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-was-highest-1-month-after-dose-two-and-subsequently-declined-but-remained-higher-than-before-vaccination-24-months-after-dose-two-

gE, glycoprotein E; IQR, interquartile range; Mo, month; RZV, recombinant zoster vaccine.
Figure based on raw data from Bastidas A, et al. JAMA. 2019;322(2):123–133.5,23

The humoral and cell-mediated immune response after vaccination with RZV remained higher than pre-vaccination at 24 months following vaccination with the second dose and was not affected by age (18–49 YOA or above 50 YOA).5,18,23

column-graphs-depicting-local-and-general-reactions-in-autologous-haematopoietic-stem-cell transplantation-patients-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-local-and-general-reactions-were-more-frequently-reported-by-those-in-the-vaccine-group-compared-with-the-placebo-group.-in-patients-who-received-the-recombinant-zoster-vaccine,-the-most-frequently-reported-local-adverse-reaction-was-pain-at-the-injection-site;-fatigue,-myalgia-and-headache-were-the-most-frequently-reported-general-reactions-

Any symptom, occurrence of the symptom regardless of intensity grade; Grade 3 pain, pain that prevented normal activity; Grade 3 redness/swelling, redness/swelling spreading beyond 100 mm of injection site; Grade 3 symptom, symptom that prevented normal activity; fever defined as a temperature (preferably oral) ≥37.5°C; Grade 3 fever >39.0°C.

GI, gastrointestinal (nausea, vomiting, diarrhoea and abdominal pain); RZV, recombinant zoster vaccine.

Figure based on raw data from Bastidas A, et al. JAMA. 2019;322(2):123-133.

Most common local and general adverse events (AEs) include pain at injection site, fatigue, and myalgia.5
Local and general symptoms occurring within 7 days of vaccination were more frequent in vaccine than in placebo recipients.5

column-graph-depicting-serious-adverse-events,-related-serious-adverse-events,-potential-immune-mediated-diseases,-fatal-serious-adverse-events,-relapses-of-underlying-diseases-and-unsolicited-adverse-events-in-autologous-haematopoietic-stem-cell-transplantation-patients-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-overall-incidences-were-similar-between-both-groups-

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Grade 3, severe AE that prevents normal activity.

AE, adverse event; auHSCT, autologous haematopoietic stem cell transplant; pIMD, potential immune-mediated disease; RZV, recombinant zoster vaccine; SAE, serious adverse event.

Figure based on raw data from Bastidas A, et al. JAMA. 2019;322(2):123–133.

Proportions of patients experiencing AEs, serious adverse events (SAEs), fatal SAEs, potential immune-mediated disease (pIMDs), and relapse of underlying disease appear to be similar between the RZV and placebo groups.5

Haematological malignancies

While or just upon receiving immunosuppressive chemotherapy7

A Phase 3, randomised, observer-blind, placebo-controlled, multi-centre study to assess the safety and immunogenicity of the adjuvanted RZV when administered intramuscularly on a two-dose schedule to adults aged 18 years and older with haematologic malignancies.7,25

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Timing of vaccination:

Ongoing/starting cancer therapy: ≥10 days before or after cancer treatment.
Completed cancer therapy course: ≥10 days to 6 months after full course.

*The second dose of vaccine/placebo administered 1 to 2 months after the first dose; **Visit 3 Month 2, contact Month 7, Visit 4 Month 13 are respectively 1, 6, 12 months post-Visit 2; †contact Month 7.

RZV, recombinant zoster vaccine; YOA, years of age.

Post hoc vaccine efficacy7

RZV Placebo VE*
95% CI
N

n

 Incidence per 1000 person years N

n

 Incidence per 1000 person years % LL UL

P

value
259 2 8.5 256 14 66.2 87.2 44.3 98.6 0.0021

*Includes all haematological malignancy subgroups.

mTVC: from 1 month post dose 2 until study end; subjects having received 2 doses of RZV.

CI, confidence interval; LL, lower limit; mTVC, modified total vaccine cohort; N, number of subjects included in each group; n, number of subjects reporting at least one event in each group; RZV, recombinant zoster vaccine; UL, upper limit; VE, vaccine efficacy.

Post hoc analysis revealed a vaccine efficacy of 87.2% against herpes zoster in this population of immunocompromised adults aged 18 years and older.7

column-graph-depicting-the-anti-glycoprotein-e-antibody-geometric-mean-concentration-in-patients-with-haematological-malignancies-pre-and-post-vaccination-with-the-recombinant-zoster-vaccine-or-placebo.-one-month-post-vaccine-dose-2,-the-geometric-mean-concentration-was-13445.6-milli-international-units-per-millilitre-in-the-recombinant-zoster-vaccine-group-and-832.0-milli-international-units-per-millilitre-in-the-placebo-group.-across-all-timepoints-up-to-month-13-post-vaccination-the-proportion-of-participants-with-anti-glycoprotein-e-antibody-geometric-mean-concentration-point-estimates-was-higher-in-the-vaccine-group-than-in-the-placebo-group-

All participants, including subjects with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia.
GMC, geometric mean concentration; Mo, month; Pre, pre-vaccination; RZV, recombinant zoster vaccine.

column-graph-depicting-the-c-d-4-plus-t-cell-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-in-patients-with-haematological-malignancies-pre-and-post-vaccination-with-the-recombinant-zoster-vaccine-or-placebo.-1-month-post-dose-2,-the-median-c-d-4-plus-t-cell-frequency-was-3081.9-in-the-vaccine-group-and-99.0-in-the-placebo-group.-up-to-13-months-post-completion-of-the-two-dose-vaccination-schedule-c-d-4-plus-t-cell-frequency-in-the-recombinant-zoster-vaccine-group-remained-more-than-15-fold-higher-compared-with-the-placebo-group-

All participants, including subjects with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia.
BCL, B-cell lymphoma; CLL, chronic lymphocytic leukaemia; IQR, interquartile range; Mo, month; RZV, recombinant zoster vaccine.

The humoral and cell-mediated immune response after vaccination with RZV persisted above baseline until Month 13 in all strata, post-vaccination.7 CMI responses were not affected by age (18–49 YOA and above 50 YOA), albeit a slight trend for stronger humoral responses was observed in the younger populations compared with above 50 YOA7,18

Reactogenicity of RZV compared with placebo7

  RZV N=278 Placebo N=274
  n % n %
Local reactions, any (Grade 3a)
  
Pain 221 (29) 79.5 (10.4) 45 (0) 16.4 (0.0)
Redness 115 (12) 41.4 (4.3) 5 (0) 1.8 (0.0)
Swelling 63 (5) 22.7 (1.8) 2 (0) 0.7 (0.0)
General reactions, any (Grade 3a)  
Fatigue 162 (23) 58.3 (8.3) 102 (10) 37.2 (3.6)
GI symptoms
 76 (9)
 27.3 (3.2) 29 (3) 10.6 (1.1)
Headache 115 (12) 41.4 (4.3) 64 (6) 23.4 (2.2)
Myalgia 122 (22) 43.9 (7.9) 48 (5) 17.5 (1.8)
Shivering 69 (11) 24.8 (4.0) 18 (0) 6.6 (0.0)
Fever 68 (3) 24.5 (1.1) 21 (1) 7.7 (0.4)

aGrade 3 solicited adverse events were defined as preventing normal activity (for headache, fatigue, gastrointestinal symptoms, myalgia, and shivering), substantial pain at rest and preventing normal everyday activities (for injection-site pain), having a surface diameter greater than 100 mm (for injection site redness and swelling), or body temperature greater than 39.0°C (for fever).

AE, adverse event; n, number of participants with at least one solicited local or general symptom documented as either present or absent; GI, gastrointestinal (nausea, vomiting, diarrhoea and abdominal pain); RZV, recombinant zoster vaccine.

Local AEs include pain, redness, and swelling.7 General AEs include fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever.7
Occurrence of unsolicited AEs was similar between vaccine and placebo groups and the AEs reported were consistent with the underlying diseases, known complications of the diseases, and the concomitant therapies.7

Safety7

 

 RZV N=283 Placebo N=279
Type of event n % n %
SAE 66 23.3 82 29.4
Related SAE 1 0.4 1 0.4
Fatal SAE 29 10.2 37 13.3
Related fatal SAE 1* 0.4 0.0 0.0
Disease-related event† 45 15.9 58 20.8
pIMDs: 3 1.1 2 0.7

Autoimmune haemolytic anaemia

 0 - 1 -

Autoimmune pancytopenia

 1 - 0 -

Gout

 1 - 0 -

Guillain-Barré syndrome

 0 - 1 -

Erythema nodosum

 1 - 0 -

*One of the related SAEs, further classified as a fatal SAE, was considered by the investigator as related to vaccination. This event was a neonatal death of the offspring of a subject who was vaccinated before estimated pregnancy onset.

†Relapse or progression of the original haematological malignancy.

N, number of subjects with at least one administered dose; n/%, number/percentage of subjects reporting the symptom at least once; pIMD, potential immune mediated disease; RZV, recombinant zoster vaccine; SAE, serious adverse event

Incidences of unsolicited or SAEs, pIMDs, disease-related events and fatal SAEs were similar between RZV and placebo groups.7

Solid tumours

Solid tumour malignancies while on immunosuppressive chemotherapy21

A Phase 2/3, randomised, observer-blind, placebo-controlled, multi-centre clinical trial to assess the immunogenicity and safety of the adjuvanted RZV when administered intramuscularly on a 0 and 1 to 2 months schedule to adults ≥18 YOA with solid tumours receiving chemotherapy (chemo).21,26,27

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study-design-to-asses-the-immunogenicity-and-safety-of-the-recombinant-zoster-vaccine-when-administered-intramuscularly-to-adults-aged-18-years-and-older-with-solid-tumours-receiving-chemotherapy.-adults-with-solid-tumours-undergoing-chemotherapy-were-randomised-four-to-four-to-one-to-one-to-receive-two-doses-of-either-the-recombinant-zoster-vaccine-or-placebo-one-to-two-months-apart.-the-first-two-groups-received-the-first-dose-between-8-and-30-days-before-the-start-of-their-chemotherapy-cycle-and-the-latter-two-groups-at-the-start-of-their-first-or-second-chemotherapy-cycle.-visits-were-carried-out-at-months-0,-1,-2,-7-and-13-and-blood-sampling-occurred-at-each-visit.- participants-were-contacted-by-telephone-between-the-last-two-visits.-the-follow-up-period-was-month-2-to-month-13-

*Blood samples were collected from a sub cohort of subjects at Visit 1, 2, 3 and 5 for cell-mediated immunity.
†Second dose administered between 1 and 2 months after the first vaccination, at the first day of a subsequent cycle of chemotherapy.
‡Visit 4 occurred within Months 4 to 13 for a blood sample at the start of the last cycle of chemotherapy (if at least 2 months after the previous blood sample).

RZV, recombinant zoster vaccine; YOA, years of age

stacked-column-chart-depicting-the-proportion-of-solid-tumour-diagnosis-in-all-study-participants.-breast-cancer-was-the-most-common-diagnosis-followed-by-colorectal-cancer-

*Includes gastric, endometrial, ovarian, head and neck, larynx, mouth, sinus, tonsil, liposarcoma myxoid, liver, oesophageal, renal, sarcoma, stomach, testicular embryonic carcinoma, thyroid, tongue, cervix, urothelial, uterine leiomyosarcoma.

RZV, recombinant zoster vaccine.

The figure has been independently created by GSK from Vink P. Poster 1349. Presented at IDWeek; 4–8 October, 2017; San Diego, CA, USA.

column-graph-depicting-the-anti-glycoprotein-e-antibody-geometric-mean-concentration-in-patients-with-solid-tumours.-one-month-post-vaccine-dose-2,-the-pooled-anti-glycoprotein-e-antibody-geometric-mean-concentration-was-18292-milli-international-units-per-milliliter-and-remained-higher-in-the-vaccine-pre-chemo-group-than-in-the-vaccine-on-chemo-group.-patients-vaccinated-before-chemotherapy-showed-higher-antibody-levels-1-month-after-dose-1-and-1-month-after-dose-2,-compared-with-those-vaccinated-while-on-chemotherapy.-however,-the-levels-were-similar-at-month-12-after-two-dose-schedule-completion-

ATP cohort for humoral immunogenicity and humoral persistence.
ATP, according-to-protocol; gE, glycoprotein; GMC, geometric mean concentration; Mo, month; PI, post-dose 1; PII, post-dose 2; Pre, pre-vaccination; RZV, recombinant zoster vaccine

Cellular immune response PRE-chemo21,26,27

 

RZV-CMI

(N=25)

Placebo-CMI

(N=30)
Frequency of gE-specific CD4+ T cells, cells/million
Month 0

Number of patients analysed

Median (IQR)

25

127.3 (49.7–192.4)

27

104.8 (27.5–151.5)
Month 1

Number of patients analysed

Median (IQR)

25

391.9 (139.7–603.7)

30

50.0 (1.0–179.4)
Month 2

Number of patients analysed

Median (IQR)

22

778.8 (393.1–1098.2)

29

61.8 (17.4–139.5)
Month 13

Number of patients analysed

Median (IQR)

18

332.9 (114.9–604.6)

19

51.2 (1.0–288.6)

Frequencies of gE-specific CD4+ T cells per 106 total CD4+ T cells (ATP subcohort for CMI, PRE-chemo groups only). 

ATP cohort for humoral immunogenicity and humoral persistence.

ATP, according-to-protocol; CMI, cell-mediated immunity; gE, glycoprotein E; Mo, month; Pre, pre-vaccination Mo 0; Q, quartile; RZV, recombinant zoster vaccine.

Humoral and CMI responses persisted 1 year after vaccination. CD4+ T cell frequencies were in similar ranges in RZV recipients 18–49 and ≥50 YOA.
Immunogenicity persisted 12 months after vaccination regardless of the timing of the first vaccination in relation to the start of chemotherapy.21,27

column-graphs-depicting-the-local-and-general-reactions-in-patients-with-solid-tumours-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-in-patients-who-received-the-recombinant-zoster-vaccine-the-most-frequently-reported-local-adverse-reaction-was-pain-at-the-injection-site;-fatigue,-myalgia-and-gastrointestinal-symptoms-were-the-most-frequently-reported-general-reactions-

Figures adapted with permission from Vink P et al. Cancer 2019;125:1301–1312.
Grade 3 pain, pain that prevented normal activity; grade 3 redness/swelling, redness/swelling spreading beyond 100 mm of injection site; grade 3 fever >39.0°C.
AE, adverse event; GI, gastrointestinal (nausea, vomiting, diarrhoea and/or abdominal pain); RZV, recombinant zoster vaccine.

Most common local and general AEs include injection site pain, fatigue, and myalgia.21,27 Solicited AEs were more frequent among RZV recipients than placebo recipients; however, the symptoms were mild to moderate in intensity and transient, with a median duration up to 4 days.21,27

column-graph-summarising-serious-adverse-events,-related-serious-adverse-events,-fatal-adverse-events,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-in-patients-with-a-solid-tumour-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-overall-incidences-of-serious-adverse-events,-deaths,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-were-similar-between-the-recombinant-zoster-vaccine-and-placebo-groups-

AE, adverse event; pIMDs, potential immune-mediated diseases; RZV, recombinant zoster vaccine; SAE, serious adverse event.
The graph has been independently created by GSK from Zoster-028 Clinical Study Report 116427. Available at: https://gsk-clinicalstudyregister.com/files2/116427-Clinical-Study-Result-Summary.pdf (accessed May 2023) and Vink P, et al. Cancer. 2019;125(8):1301–1312.

The proportions of patients experiencing AEs, SAEs and fatalities appear to be similar between the RZV and placebo groups.21 Frequency of solicited general symptoms in both the RZV arm and especially the placebo arm were higher than in patients with solid tumours compared with immunocompetent older adults, likely reflecting a higher background rate of general symptoms associated with underlying malignancy and treatment.21

Renal transplants

Post-renal transplant20

A Phase 3, randomised, observer-blind, placebo-controlled, multi-centre clinical study to assess the immunogenicity and safety of the adjuvanted RZV vaccine when administered intramuscularly on a 0 and 1 to 2 months schedule to adults ≥18 YOA upon renal transplantation.20,29–31

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*The second dose of vaccine/placebo will be administered 1 to 2 months after the first dose.
†Month 2 (Visit 3), Month 7 (Visit 4) and Month 13 (Visit 5) occurred within 1, 6 and 12 months of the second vaccination, respectively. RZV, recombinant zoster vaccine; YOA, years of age.

column-graph-depicting-the-humoral-vaccine-response-rate-in-renal-transplant-patients-stratified-by-age,-specifically-18-to-49-years-of-age-and-those-aged-50-years-and-older.-The-humoral-vaccine-response-rate-in-the-vaccine-group-was-approximately-70-to-80-percent-at-month-2-in-both-age-groups.-at-each-time-point-up-to-the-13-month-of-follow-up,-humoral-vaccine-immune-responses-appeared-higher-in-the-18-to-49-years-of-age-cohort-than-in-the-50-years-and-older-cohort.-post-vaccination,-the-vaccine-response-rate-in-the-placebo-group-remained-near-pre-vaccination-level-

Humoral response was measured at Mo 2, Mo 7 and Mo 13, which occurred within 1, 6 and 12 months of the second vaccination, respectively.
Mo, month; RZV, recombinant zoster vaccine; VRR, vaccine response rate; YOA, years of age.
Reproduced from Vink P et al .2020 under the terms of a Creative Commons CC-BY licence (http://creativecommons.org/licenses/by/4.0/).

column-graph-depicting-the-vaccine-response-rate-for-cell-mediated-immune-responses-in-renal-transplant-patients-stratified-by-age,-specifically-18-to-49-years-of-age-and-those-aged-50-years-or-older.-The-vaccine-response-rate-for-cell-mediated-immune-response-in-the-vaccine-group-at-month-2-was-approximately-80-percent-and-60-percent-in-18-to-49-years-of-age-cohort-and-the-50-years-and-older-cohort-respectively.-at-each-time-point,-cell-mediated-immune-responses-appeared-to be-higher-in-the-18-to-49-years-of-age-cohort-compared-to-the-50-years-and-older-cohort.-cell-mediated-immune-vaccine-response-rates-in-the-placebo-group-remained-near-the-pre-vaccination-level-

Cell-mediated immune response was measured at Mo 2 and Mo 13, which occurred within 1 and 12 months of the second vaccination, respectively.
CMI, cell-mediated immunity; Mo, month; RZV, recombinant zoster vaccine; VRR, vaccine response rate; YOA, years of age
Reproduced from Vink P et al .2020 under the terms of a Creative Commons CC-BY licence (http://creativecommons.org/licenses/by/4.0/).

Vaccine response rate for humoral immunogenicity was 80.2% at Month 2 and 66.7% at Month 13. At each time point, humoral and cellular immune responses appeared higher in the 18–49 YOA cohort than in the ≥50 YOA cohort.
Independent of age, RZV induced robust humoral and CMI responses to gE when administered 4–18 months after renal transplantation.20

column-graph-depicting-the-local and general reactions in-renal-transplant patients-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-in-patients-who-received-the-recombinant-zoster-vaccine,-the-most-frequently-reported-local-adverse-reaction-was-injection-site-pain;-fatigue,-myalgia-and-headache-were-the-most-frequently-reported-general-reactions-

Grade 3 pain defined as significant pain at rest and preventing normal activity; grade 3 redness and swelling defined as surface diameter >100 mm. Fever defined as ≥37.5°C; Fever was not graded in this study. Fever >39.0°C presented as grade 3.
For all others, grade 3 AEs defined as preventing normal activity.

AE, adverse event; GI, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain); RZV, recombinant zoster vaccine.

Graphs reproduced from Vink P et al .2020 under the terms of a Creative Commons CC-BY licence (http://creativecommons.org/licenses/by/4.0/), with additional data from ClinicalTrials.gov. NCT02058589.

Most common local and general AEs include injection site pain, fatigue, and myalgia.9 Solicited AEs were primarily mild to moderate and transient in nature. Overall, reactogenicity was acceptable and as expected for the patient conditions.20

column-graph-summarising-serious-adverse-events,-related-serious-adverse-events,-fatal-adverse-events,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-in-renal-transplant-patients-who-received-either-the-recombinant--zoster-vaccine-or-placebo.-overall-incidences-of-serious-adverse-events,-deaths,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-were-similar-between-the-recombinant-zoster-vaccine-and-placebo-groups-

AE, adverse event; pIMD, potential immune-mediated disease; RZV, recombinant zoster vaccine; SAE, serious adverse event.
The graph has been independently created by GSK from Vink P, et al. Clin Infect Dis. 2020;70(2):181–190.

No apparent differences were observed between RZV and placebo groups in the occurrence of unsolicited AEs, SAEs (including fatalities), pIMDs, biopsy-proven allograft rejections, or allograft function changes.20

Human immunodeficiency virus (HIV)

People living with HIV19

A Phase 1/2a randomised, observer-blind, placebo-controlled, multi-centre study to evaluate the safety and immunogenicity of GSK Biologicals’ adjuvanted RZV, in comparison with placebo when administered as 3 doses to adults infected with HIV.19,32

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study-design-to-evaluate-the-safety-and-immunogenicity-of-the-recombinant-zoster-vaccine-in-comparison-with-placebo-when-administered-in-a-three-dose-schedule-to-adult-h-i-v-infected-subjects.-94-recipients-recieved-anti-retroviral-therapy-with-a-c-d-4-plus-t-cell-count-of-greater-than-or-equal-to-200-cells-per-cubic-millimetre;-14-recipients-recieved-anti-retroviral-therapy-with-a-c-d-4-plus-t-cell-count-between-50-and-199-cells-per-cubic-millimetre;-15-recipients-recieved-anti-retroviral-therapy-with-a-c-d-4-plus-t-cell-count-of-greater-than-or-equal-to-500-cells-per-cubic-millimetre.-vaccination-occurred-at-months-0,-2-and-6.-blood-sampling-occurred-at-months-0,-1,-2,-3,-6,-7-and-18.

ART, anti-retroviral therapy; HIV, human immunodeficiency virus; RZV, recombinant zoster vaccine.
The figure is adapted with the permission of Oxford University Press. It was first published in Berkowitz EM, et al. 2015. J Infect Dis. 211(8):1279–1287.

line-graph-depicting-the-anti-glycoprotein-e-antibody-geometric-mean-concentration-in-patients-infected-with-h-i-v.-the-anti-glycoprotein-e-antibody-geometric-mean-concentration-remained-above-pre-vaccination-concentrations-up-to-18-months-post-final-recombinant-zoster-vaccine-dose,-whereas-anti-glycoprotein-e-antibody-geometric-mean-concentrations-in-the-placebo-group-remained-at-pre-vaccination-level-throughout-the-study-

Figure adapted with permission from Berkowitz EM et al. J Infect Dis 2015;211:1279–1292.
*Humoral response was defined as a ≥4-fold increase in GMC in subjects who were seropositive before vaccination or a GMC ≥4 times the cut-off value in subjects seronegative before vaccination.
gE, glycoprotein E; GMC, geometric mean concentration; Mo, month; Pre, pre-vaccination; RZV, recombinant zoster vaccine.

line-graph-illustrating-the-median-c-d-4-plus-t-cell-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-in-patients-infected-with-the-human-immunodeficiency-virus.-in-the-recombinant-zoster-vaccine-group-c-d-4-plus-t-cell-frequency-peaked-1-month-post-dose-2-but-did-not-increase-further-after-the-third-dose.-the-median-frequency-of-glycoprotein-e-specific-c-d-4-plus-t-cells-for-the-placebo-group-remained-at-pre-vaccination-level-throughout-the-study-

Figure adapted with permission from Berkowitz EM et al. J Infect Dis 2015;211:1279–1292.
CMI, cell-mediated immunity; gE, glycoprotein E; Mo, month; Pre, pre-vaccination; RZV, recombinant zoster vaccine.

The humoral and cell-mediated immune responses after vaccination with RZV were similar to those seen in healthy adults ≥50 years of age after the second dose. The administration of a third dose did not show substantial additional benefit over two doses in terms of gE-specific humoral and cell-mediated immune responses.19 One year after vaccination, the gE-specific CD4+ T cell responses were higher than those seen 1 month after natural herpes zoster episodes.19

column-graph-summarising-the-local-and-general-reactions-in-patients-infected-with-h-i-v-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-local-and-general-reactions-were-more-frequently-reported-by-those-in-the-vaccine-group-compared-with-the-placebo-group.-in-patients-who-received-the-recombinant-zoster-vaccine-the-most-frequently-reported-local-reaction-was-injection-site-pain;-the-most-frequently-reported-general-reaction-was-fatigue,-followed-by-myalgia-and-headache-

Graph adapted from data in Berkowitz EM, et al. J Infect Dis. 2015;211(8):1279–1287.
†Grade 3 reactions defined as AEs that prevent normal everyday activities (grade 3 redness and swelling is defined as ≥100 mm; grade 3 fever is defined as an oral/axillary temperature of >39.0°C).
AE, adverse event; GI, gastrointestinal (nausea, vomiting, diarrhoea and abdominal pain); RZV, recombinant zoster vaccine.

Most common local and general AEs include pain at injection site, fatigue, and myalgia.19 Those reactions were transient and did not impact study compliance.19

column-graph-showing-serious-adverse-events,-related-serious-adverse-events,-fatal-adverse-events,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-in-h-i-v-infected-adults-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-there-were-no-reported-incidences-of-related-serious-adverse-events,-fatal-adverse-events-and-potential-immune-mediated-diseases-during-the-entire-study-period.-serious-adverse-events-and-unsolicited-adverse-events-were-similar-between-the-recombinant-zoster-vaccine-and-placebo-groups-

The graph has been independently created by GSK from Berkowitz EM, et al. J Infect Dis. 2015;211(8):1279–1287.
AE, adverse event; HIV, human immunodeficiency virus; pIMD, potential immune-mediated disease; RZV, recombinant zoster vaccine; SAE, serious adverse event.

RZV was generally well tolerated in people infected with HIV. No vaccination-related SAEs, deaths, or new onsets of immune-mediated inflammatory diseases were reported. Furthermore, RZV had no sustained impact on either HIV ribonucleic acid (RNA) concentration or CD4+ T cell counts over the 18 month study period.19

Conclusion

Across all five randomised, placebo-controlled studies including patients with a wide variety of immunocompromising conditions receiving multiple immunosuppressive medications, RZV induced robust and persistent humoral and cellular immune responses.

The CMI response, the mechanistic driver for protection against herpes zoster, was not affected by the underlying diseases presented and was maintained for at least one year at levels similar to those observed in immunocompetent older adults above 50 YOA. Furthermore, age (18–49 YOA or above 50 YOA) did not affect the magnitude of CMI responses in people with auHSCT, haematological malignancy, renal transplant, and solid tumour populations.

An efficacy of 68.2% was demonstrated in people with auHSCT and 87.2% in people with a haematogical malignancy, the latter in a post hoc analysis. Although no efficacy data are available for people with solid tumour or renal transplants, mounted CMI responses were robust and similar to those evaluated in people with auHSCT and haematological malignancies, indicating a similar clinical benefit.5,7,18–21

Abbreviations

AE, adverse event; ART, anti-retroviral therapy; ATP, according to protocol; BCL, B-cell lymphoma; CLL, chronic lymphocytic leukaemia; CMI, cell-mediated immunity; gE, glycoprotein E; GI, gastrointestinal; GMC, geometric mean concentration; HIV, human immunodeficiency virus; IQR, interquartile range; LL, lower limit; Mo, month; mTVC, modified total vaccinated cohort; pIMD, potential immune-mediated disease; PHN, post-herpetic neuralgia; Pre, pre-vaccination; Q, quartile; RNA, ribonucleic acid; RZV, recombinant zoster virus; SAE, serious adverse event; TVC, total vaccinated cohort; UL, upper limit; VE, vaccine efficacy; VRR, vaccine response rate; YOA, years of age.

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NX-GBL-SGX-WCNT-230001 | September 2023