Shingles-science-image Shingles-science-image

Co-administration of the recombinant zoster vaccine (RZV) with other adult vaccines

Throughout life, vaccines are recommended to protect individuals from vaccine-preventable diseases. With an increasing number of adult immunisation recommendations, the below overview aims to guide health care professionals (HCPs) in their daily practice routine on how to combine vaccination of RZV with other adult vaccines.

Co-administration can reduce the number of missed vaccination opportunities, ensure the timely administration of vaccines and thereby increase vaccination coverage rates.1 Scientific data covering the safety, immunogenicity and real-world evidence for individual vaccines when administered concomitantly with RZV are summarised below.

Overview of clinical studies where RZV was co-administered with other adult vaccines

Co-administered Vaccine
Quadrivalent Seasonal Inactivated Influenza Vaccine (IIV4)2 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23)3 13-Valent Pneumococcal Conjugate Vaccine (PCV13)4 Tetanus, Diphtheria and acellular Pertussis Vaccine (Tdap)5 mRNA-1273 Booster6
Conclusion
Co-administration showed no safety concerns and no evidence for interference in the immune response to any of the antigens in either vaccine.2 Co-administration showed no safety concerns and no evidence for interference in the immune response to any of the antigens in either vaccine.3 Co-administration 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.4 Co-administration showed no safety concerns and met non-inferiority for the immune responses to the antigens in either vaccine, except PRN antigen in Tdap.5
Data do not suggest a clinically relevant interference between RZV and Tdap.5		 Co-administration showed no safety concern and no evidence for interference in the immune response to any of the antigens in either vaccine.6

Design and Schedule2–6

  • Randomised, open-label, phase III clinical trials
  • Eligible participants were healthy adults aged ≥ 50 years
  • Participants were randomised in a 1:1 ratio to concomitant administration of RZV plus the co-administered vaccine or sequential administration of the two vaccines
Design and Schedule Flow Chart

*For the sequential administration of the mRNA-1273 vaccine booster, RZV was administred 2- and 10-weeks post mRNA-1273 administration. In all other trials, RZV was administered after 2 months post IIV4, Tdap, PPSV23, or PCV13 administration. Second dose of RZV was administered 2 months post first RZV dose in all trials.2–6

Co-Ad, co-administration; IIV4, quadrivalent seasonal inactivated influenza vaccine; mRNA-1273, COVID-19 messenger ribonucleic acid-1273 vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine; PRN, pertactin; RZV, recombinant zoster vaccine; Tdap, reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine.

Immune responses to RZV were consistently similar when RZV was co-administered or administered sequentially with other adult vaccines7

Humoral immune response to RZV when co-administered or administered sequentially with other routine adult vaccines7

Error bars show 95% CI.

Anti-gE, varicella zoster virus anti-glycoprotein E antibodies; CI, confidence intervals; GMC, geometric mean concentration; mRNA-1273, COVID-19 messenger ribonucleic acid-1273 vaccine; IIV4, quadrivalent seasonal inactivated influenza vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine; Tdap, reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine; PCV13, 13-valent pneumococcal conjugate vaccine.

  • Across all five analysed trials, similar consistent humoral immune responses to RZV were observed, irrespective if administered concomitantly or sequentially with other routinely administered adult vaccines.
  • Concomitant administration of RZV did not substantially alter the immunogenicity of IIV4, PPSV23, Tdap (except pertactin)*, PCV13 and mRNA-1273.2–7

*The clinical significance of this finding remains unclear.

Reactogenicity and safety profile of RZV when co-administered or administered sequentially with other adult vaccines2–8

Local reactions7

Solicited local adverse events, any and Grade 3, after RZV

Incidence of any and Grade 3 solicited local events occurring ≤7days after administration of RZV. Solicited local adverse events include injection site pain, redness, and swelling.

ZOE-50, pivotal trial for RZV in patients equal and above 50 years of age (YOA); Co-ad, co-administration of vaccines; mRNA-1273, COVID-19 messenger ribonucleic acid-1273 vaccine; IIV4, quadrivalent seasonal inactivated influenza vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine; RZV, recombinant zoster vaccine; Seq, sequential administration of vaccines; Tdap, reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine.

  • Across all five trials, the most common local reaction after administration of RZV was injection site pain. Concomitant vaccination was well tolerated by all trial participants.2–6
  • Similar local reactogenicity was observed in the pivotal ZOE-50 clinical trial, where RZV was administered to individuals 50 years and older.

General reactions2–8

Solicited systemic adverse events, any and Grade 3, after RZV

Incidence of solicited systemic events of any severity and grade 3 solicited systemic events occurring ≤7days after administration of RZV. Solicited general reactions include arthralgia, fatigue, fever, gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), headache, myalgia, and shivering.

ZOE-50, pivotal trial for RZV in patients equal and above 50 years of age (YOA); Co-ad, co-administration of vaccines; mRNA-1273, COVID-19 messenger ribonucleic acid-1273 vaccine; IIV4, quadrivalent seasonal inactivated influenza vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine; RZV, recombinant zoster vaccine; Seq, sequential administration of vaccines; Tdap, reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine.

  • Of all general reactions, myalgia was the most commonly reported systemic adverse event (AE), irrespective of concomitant or sequential administration.
  • The overall incidence of systemic solicited AEs reported within 7 days of vaccination was generally similar after concomitant and sequential administration of RZV with other routinely administered adult vaccines.2–7
  • Incidence of systemic solicited AEs was similar to what has been observed in the pivotal ZOE-50 clinical trial, where RZV was administered to individuals equal and above 50 years of age (YOA).8,9

Unsolicited adverse events following RZV co-administration with other vaccines:7

  • The overall incidence of unsolicited AEs reported within 30 days of vaccination was generally similar after co-administration and sequential administration of RZV with other adult vaccines.
  • A minority of these events were considered to be vaccine-related.
  • Most frequently reported unsolicited AEs related to vaccination across study groups included injection-site pruritus, arthralgia, headache and diarrhea.

Real-world effectiveness of RZV when co-administered with other routinely administered adult vaccines10

In the below summarised real-world effectiveness study, the risk for herpes zoster (HZ) was evaluated upon concomitant vaccination of RZV with other routinely administered adult vaccines. Electronic health records (EHR) from Kaiser Permanente Southern California (KPSC) were analysed.

One of the advantages of utilizing the EHR from KPSC is represented in the diverse sociodemographic characteristics of its more than 4.7 million enrolees above 50 YOA across several countries in California representing the underlying population. Of 41,251 enrolled individuals, 12,898 received RZV concomitant with other vaccines, whereas 28,353 RZV recipients did not receive other concomitant vaccination.10

The below graphic summarises the study design and provides a population overview, stratified by age.10

Study design10

*"At index date" defines the age range of patients at the time when they received the second dose of RZV; †co-administration was defined as receipt of any vaccine on the same day as either dose of RZV; ‡individuals that received ZVL within the last 5 years prior to vaccination with RZV.

Figure created by GSK from the original data presented in Bruxvoort KJ, et al. Open Forum Infect Dis. 2022;9(3):ofac011.

Co-Ad, co-administration; HZ, herpes zoster; N, number of participants; RZV, recombinant zoster vaccine; YOA, years of age; ZVL, zoster vaccine live.

In the majority of cases influenza vaccine was the most common co-administered vaccine with RZV, followed by pneumococcal, tetanus diphtheria (Td)/Tdap, hepatitis or other adult vaccines.10

Most common vaccines co-administered* with RZV (N=12,898)10

*Defined as receipt of any vaccine on the same day as either dose of RZV; †adjuvanted vaccines included adjuvanted influenza or hepatitis B vaccine.

Figure created by GSK from the original data presented in Bruxvoort KJ, et al. Open Forum Infect Dis. 2022;9(3):ofac011.

RZV, recombinant zoster vaccine; Td, tetanus and diphtheria vaccine; Tdap, tetanus, diphtheria and acellular pertussis vaccine.

The effectiveness of RZV in the prevention of HZ was not significantly different between recipients of RZV alone or RZV concomitantly administered with other adult vaccines.10

Herpes zoster incidence rate in individuals with and without concomitant vaccination10

*Defined as receipt of any vaccine on the same day as either dose of RZV; †the number of HZ cases was 136, 41, 22, 14 and 5 for patients receiving RZV without concomitant, with concomitant vaccine, at first dose of concomitant vaccine, at second dose of concomitant vaccine and at both doses of concomitant vaccine, respectively; ‡the total number of PYs was 40,297, 18,328, 9772, 7006 and 1550 for patients receiving RZV without concomitant, with concomitant vaccine, at first dose of concomitant vaccine, at second dose of concomitant vaccine and at both doses of concomitant vaccine, respectively.

Figure created by GSK from the original data presented in Bruxvoort KJ, et al. Open Forum Infect Dis. 2022;9(3):ofac011.

Co-Ad; co-administration; CI, confidence interval; HZ, herpes zoster; PY, person-year; RZV, recombinant zoster vaccine; Td, tetanus & diphtheria vaccine; Tdap, tetanus, diphtheria and acellular pertussis vaccine.

Co-administration of RZV with other adult vaccines: Summary

  • Across the five trials, immune responses to RZV were consistently similar when co-administered or sequentially administered with other adult vaccines. Antibody responses to Tdap, PPSV23 or PCV13 were not impacted by the co-administration of RZV (except for a reduced response to pertactin, with unclear clinical significance).2–7
  • RZV was well tolerated by participants in all five studies. No new safety signals were detected and the overall incidence of solicited and unsolicited AEs was similar after concomitant and sequential administration of the five routinely administered adult vaccines.2–7
  • RZV effectiveness in the prevention of HZ was not influenced by co-administration with other vaccines, supporting the recommendation of concomitant administration as an efficient intervention to protect more people from vaccine-preventable diseases.7,10

If you would like to read more about the studies, please follow the links below.

Co-administration of RZV with seasonal quadrivalent inactivated influenza vaccine (IIV4)2

NCT01954251

PUBMED.

Co-administration of RZV with 23-valent pneumococcal polysaccharide vaccine (PPSV23)3

NCT02045836

PUBMED.

Co-administration of RZV with 13-valent pneumococcal conjugate vaccine (PCV13)4

NCT03439657

PUBMED.

Co-administration of RZV with Tetanus, Diphtheria and acellular Pertussis Vaccine (Tdap)5

NCT02052596

PUBMED.

Co-administration of RZV with COVID-19 messenger ribonucleic acid-1273 vaccine booster (mRNA-1273)6

NCT05047770

PUBMED.

Abbreviations

AE, adverse event; anti-gE, varicella zoster virus anti-glycoprotein E antibodies; CI, confidence interval; Co-Ad, co-administration; EHR, electronic health records; GMC, geometric mean concentration; HCP, health care professional; HZ, herpes zoster; mRNA-1273, COVID-19 messenger ribonucleic acid-1273 vaccine; IIV4, quadrivalent seasonal inactivated influenza vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine; PRN, pertactin; PY, person-year; RZV, recombinant zoster vaccine; Td, tetanus and diphtheria vaccine; Tdap, reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine; YOA, years of age; ZVL, zoster vaccine live.

References

  1. Bonanni P, et al. Hum Vaccin Immunother. 2023;19(1):2195786.
  2. Schwarz TF, et al. J Infect Dis. 2017;216(11):1352–1361.
  3. Maréchal C, et al. Vaccine. 2018;36(29):4278–4286.
  4. Min JY, et al. J Infect. 2022;84(4):490–498.
  5. Strezova A, et al. Vaccine. 2019;37(39):5877–5885.
  6. Naficy A, et al. Clin Infect Dis. 2023;10.1093/cid/ciad361.
  7. Ali O, et al. Vaccine. 2023, submitted.
  8. Lal H, et al. N Engl J Med. 2015;372(22):2087–2096.
  9. European Medicines Agency (EMA). Shingrix summary of product characteristics (SmPC). https://www.ema.europa.eu/documents/product-information/shingrix-epar-product-information_en.pdf Accessed September 2023.
  10. Bruxvoort KJ, et al. Open Forum Infect Dis. 2022;9(3):ofac011.

©2023 GSK group of companies. All rights reserved.

NX-GBL-SGX-WCNT-230002 | October 2023