Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults

Schwarz, Tino F.; Volpe, Stéphanie; Catteau, Grégory; Chlíbek, Roman; David, Marie Pierre; Richardus, Jan Hendrik; Lal, Himal; Oostvogels, Lidia; Pauksens, Karlis; Ravault, Stéphanie; Rombo, Lars; Sonder, Gerard J.B.; Smetana, Jan; Heineman, Thomas C.; Bastidas, Adriana

doi:10.1080/21645515.2018.1442162

Cited by 63 publications

(62 citation statements)

References 25 publications

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“…This study showed that the initial increase in VZV-specific immune markers declined over the first 48 months after vaccination. However, cell-mediated and humoral response plateaued after 4 years after vaccination to a level at least threefold above the pre-vaccination level and remained stable throughout year 9 [ 39 ]. No suspected case of HZ was reported during this extension study.…”

Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness of the Adjuvant Recombinant Zoster Vaccine in Japanese Adults Aged 65 Years and Older

Shiragami

Mizukami²,

Kaise³

et al. 2019

Dermatol Ther (Heidelb)

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Introduction The incidence of herpes zoster (HZ) rises steeply after the age of 50 years and the number of HZ cases and complications such as postherpetic neuralgia (PHN) is predicted to increase because of the ageing population. The objective of this study was to estimate the cost-effectiveness of recombinant zoster vaccine (RZV) compared with no vaccine for the Japanese population aged ≥ 65 years. Methods A multi-cohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of 1 million people aged ≥ 65 years over their remaining lifetime. Vaccination at ≥ 65 years was used in alignment with the influenza and pneumococcal vaccines recommended from 65 years. Japan-specific data inputs for the model were obtained from local data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% with a second dose compliance of 95%. Costs and outcomes were discounted at 2% annually and the incremental cost-effectiveness ratio (ICER) was calculated from both a payer’s and the societal perspective. Sensitivity analyses were carried out to explore the overall uncertainty in the model. Results Vaccination with RZV was projected to prevent 48,943 HZ cases and 12,136 PHN cases per million people aged ≥ 65 years compared with no vaccination. The incremental costs and quality-adjusted life years (QALYs) gained were ¥9.99 billion and 2314 QALYs from a payer’s perspective and ¥9.34 billion and 2314 QALYs from a societal perspective. The resulting ICERs were approximately ¥4,320,000 and ¥4,040,000 per QALY gained from a payer’s and the societal perspective, respectively. The ICER remained below a willingness-to-pay threshold of ¥5,000,000 for most sensitivity analyses carried out. Conclusion Vaccination against HZ with RZV would be cost-effective compared with no vaccination for the Japanese population aged ≥ 65 years. Trial Registration GSK study identifier: HO-16-17837. Funding GlaxoSmithKline Biologicals SA. Electronic supplementary material The online version of this article (10.1007/s13555-019-0291-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness of the Adjuvant Recombinant Zoster Vaccine in Japanese Adults Aged 65 Years and Older

Shiragami

Mizukami²,

Kaise³

et al. 2019

Dermatol Ther (Heidelb)

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“…In an extension study of the original phase II trials reported by Chlibek et al (2014Chlibek et al ( , 2016, it was observed that HZ/ su induces cell mediated and humoral immunity persisting up to 9 years post initial vaccination in adults > 60 years old, confirming statistical prediction models based on immune responses measured at earlier time points. Immune responses are predicted to persist up to 15 years after the initial vaccination (Schwarz et al, 2018). The acceptable benefit/ risks profile led to the licensing by the U.S. Food and Drug Administration (FDA) in 2017 of the HZ/su vaccine (Shingrix™) and a marketing authorization valid throughout the EU on 21 March 2018 (Shingrix, INN-herpes zoster vaccine.…”

Section: Herpes Zostermentioning

confidence: 99%

Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review

2019

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Background: Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a coadministered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose: The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called adjuvant systems (AS). Furthermore, the most relevant clinical applications will be presented. Methods: A literature search covering the period 2014-2018 was performed using electronic databases from Sci finder, Science direct, Medline/Pubmed, Scopus, Google scholar. Results: Insights into the mechanism of action of QS-21 can be summarized as follows: 1) in vivo stimulation of Th2 humoral and Th1 cell-mediated immune responses through action on antigen presenting cells (APCs) and T cells, leading to release of Th1 cytokines participating in the elimination of intracellular pathogens. 2) activation of the NLRP3 inflammasome in mouse APCs with subsequent release of caspase-1 dependent cytokines, Il-1β and Il-18, important for Th1 responses. 3) synthesis of nearly 50 QS-21 analogs, allowing structure/activity relationships and mechanistic studies. 4) unique synergy mechanism between monophosphoryl lipid A (MPL A) and QS-21, formulated in a liposome (AS01) in the early IFN-γ response, promoting vaccine immunogenicity. The second part of the review is related to phase I-III clinical trials of QS-21, mostly formulated in ASs, to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases, e.g. malaria, herpes zoster, tuberculosis, AIDS and therapeutic vaccines against cancer and Alzheimer's disease. Conclusion: The most advanced phase III clinical applications led to the development of two vaccines containing QS-21 as part of the AS, the Herpes Zoster vaccine (HZ/su) (Shingrix™) which received a license in 2017 from the FDA and a marketing authorization in the EU in 2018 and the RTS,S/AS01 vaccine (Mosquirix™) against malaria, which was approved by the EMA in 2015 for further implementation in Sub-Saharan countries for routine use.2014 have made the research on vaccines very attractive in the last decades (Lee and Nguyen, 2015). Modern subunit vaccines comprising homogeneous molecular antigens have been developed to prevent and treat many human diseases, but they are weakly immunogenic and must be administered with an adjuvant to elicit a potent immune response. Adjuvants whose name originates from the Latin word adjuvare https://doi.

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“…The kinetics of gE-specific T cell responses were comparable to VZVspecific responses induced by the live-attenuated vaccine, but overall the immune response was stronger after the recombinant vaccine (86). Previous studies have also demonstrated a slight decrease of T cell, but not antibody responses with age (100-102) and gE-specific CD4 + T cell responses substantially above pre-vaccination levels for at least 9 years (103). In summary, the adjuvanted recombinant HZ vaccine seems to overcome the deleterious effects of immunosenescence and shows that a single antigen from a complex pathogen is sufficient to induce high levels of protection (104).…”

Section: Using a Recombinant Herpes Zoster Antigen With An Adjuvantmentioning

confidence: 52%

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

Wagner

Weinberger

2020

Front. Immunol.

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Infectious diseases are a major cause for morbidity and mortality in the older population. Demographic changes will lead to increasing numbers of older persons over the next decades. Prevention of infections becomes increasingly important to ensure healthy aging for the individual, and to alleviate the socioeconomic burden for societies. Undoubtedly, vaccines are the most efficient health care measure to prevent infections. Age-associated changes of the immune system are responsible for decreased immunogenicity and clinical efficacy of most currently used vaccines in older age. Efficacy of standard influenza vaccines is only 30-50% in the older population. Several approaches, such as higher antigen dose, use of MF59 as adjuvant and intradermal administration have been implemented in order to specifically target the aged immune system. The use of a 23-valent polysaccharide vaccine against Streptococcus pneumoniae has been amended by a 13-valent conjugated pneumococcal vaccine originally developed for young children several years ago to overcome at least some of the limitations of the T cell-independent polysaccharide antigens, but still is only approximately 50% protective against pneumonia. A liveattenuated vaccine against herpes zoster, which has been available for several years, demonstrated efficacy of 51% against herpes zoster and 67% against post-herpetic neuralgia. Protection was lower in the very old and decreased several years after vaccination. Recently, a recombinant vaccine containing the viral glycoprotein gE and the novel adjuvant AS01B has been licensed. Phase III studies demonstrated efficacy against herpes zoster of approx. 90% even in the oldest age groups after administration of two doses and many countries now recommend the preferential use of this vaccine. There are still many infectious diseases causing substantial morbidity in the older population, for which no vaccines are available so far. Extensive research is ongoing to develop vaccines against novel targets with several vaccine candidates already being clinically tested, which have the potential to substantially reduce health care costs and to save many lives. In addition to the development of novel and improved vaccines, which specifically target the aged immune system, it is also important to improve uptake of the existing vaccines in order to protect the vulnerable, older population.

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Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults

Cited by 63 publications

References 25 publications

Cost-Effectiveness of the Adjuvant Recombinant Zoster Vaccine in Japanese Adults Aged 65 Years and Older

Cost-Effectiveness of the Adjuvant Recombinant Zoster Vaccine in Japanese Adults Aged 65 Years and Older

Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

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