Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults

Chlíbek, Roman; Pauksens, Karlis; Rombo, Lars; Rijckevorsel, Gini van; Richardus, Jan Hendrik; Plassmann, Georg; Schwarz, Tino F.; Catteau, Grégory; Lal, Himal; Heineman, Thomas C.

doi:10.1016/j.vaccine.2015.09.073

Cited by 107 publications

(87 citation statements)

References 21 publications

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“…1 and Table 1), subsequent experiments focused on Alhydrogel and GLA-LSQ, two clinically relevant adjuvants that generated significant differences in the Pfs25-specific humoral response. Furthermore, the selection of GLA-LSQ as the main comparator to Alhydrogel is supported by the fact that another liposome-based adjuvant system containing a TLR4 agonist and QS21 has been recently approved for clinical use23 and shown to promote durable adaptive immune responses in human vaccine trials2425.…”

Section: Resultsmentioning

confidence: 99%

Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate

Radtke¹,

Anderson²,

Riteau

et al. 2017

Sci Rep

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Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum. Currently, the conjugate vaccine Pfs25-EPA/Alhydrogel is in Phase 1 clinical trials in the USA and Africa. Thus far, it has proven to be safe and immunogenic, but it is expected that a more potent formulation will be required to establish antibody titers that persist for several malaria transmission seasons. We sought to determine the contribution of carrier determinants and adjuvants in promoting high-titer, long-lived antibody responses against Pfs25. We found that both adjuvants and carrier proteins influence the magnitude and capacity of Pfs25-specific humoral responses to remain above a protective level. Furthermore, a liposomal adjuvant with QS21 and a TLR4 agonist (GLA-LSQ) was especially effective at inducing T follicular helper (Tfh) and LLPC responses to Pfs25 when coupled to immunogenic carrier proteins.

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Section: Resultsmentioning

confidence: 99%

Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate

Radtke¹,

Anderson²,

Riteau

et al. 2017

Sci Rep

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“…2,18,19 An investigational herpes zoster subunit vaccine (HZ/su; GSK Vaccines) containing VZV glycoprotein E and the AS01 B adjuvant system is being evaluated for the prevention of herpes zoster and postherpetic neuralgia in adults 50 years of age or older. [20][21][22][23][24][25] A previous trial (Zoster Efficacy Study in Adults 50 Years of Age or Older showed that HZ/su had a vaccine efficacy against herpes zoster of 97.2%, which was consistent across all age groups. 26 Although 24% of the participants in ZOE-50 were 70 years of age or older, the trial was not intended to definitively assess vaccine efficacy against herpes zoster or postherpetic neuralgia in this age group.…”

mentioning

confidence: 88%

“…30,31 Accordingly, HZ/su induces strong glycoprotein E-specific immune responses, including CD4+ T-cell responses, that are preserved with age. 20,24 Moreover, the robustness of the immune responses to glycoprotein E are attributable to the action of the AS01 B adjuvant system, which has also been shown to enhance CD4+ T-cell and humoral immune responses to subunit antigens from other pathogens. 32,33 Together, these results suggest that such adjuvants have the potential to improve the efficacy of vaccines that are intended for use in older adults and other populations that may otherwise have a lower response to vaccination.…”

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confidence: 99%

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older

Lal²,

et al. 2016

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BACKGROUNDA trial involving adults 50 years of age or older showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01 B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older . METHODSThis randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTSIn ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONSIn our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. ( 1020T h e ne w e ngl a nd jou r na l o f m e dicine H erpes zoster, or shingles, results from the reactivation of latent varicellazoster virus (VZV) and typically manifests as a vesicular, painful dermatomal rash.

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“…Few better remedies were available up to 50 years ago, since when antiviral agents and a moderately effective live-attenuated vaccine for prophylaxis have been developed. But hopefully, perhaps as a result of developments in new vaccines,1 and what appear to be prolonged immune responsiveness and safety of such vaccines,24 herpes zoster—and its often chronic, painful sequel of postherpetic neuralgia—will become diseases of the past.…”

Section: ‘Zoster’ ‘Schingles’ and Their Treatmentmentioning

confidence: 99%

Whence ‘zoster’? The convoluted classical origins of a sometimes illogical term

Schott

2016

Med Humanities

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The term 'zoster' is nowadays associated with 'herpes zoster', the condition resulting from reactivation of the latent varicella-zoster virus which causes shingles. But in antiquity the meaning of 'zoster', a Latin word originating from the Greek for a belt or girdle, was variously associated in men with a form of body armour which could enclose just one half of the body; in women with a garment worn around the waist and sometimes called a 'zona'; and with a place, Zoster, linked mythologically then with the goddess Leto and her zona. Around 48 AD, the Roman physician Scribonius Largus became the first to associate 'zona' with 'herpes', and to attribute a medical meaning to 'zona', here an abbreviation of 'zona ignea' ('fiery girdle'). Although in the past the terms 'zoster' and 'zona' were sometimes used interchangeably, today only 'zoster' remains-even when etymologically illogical in those patients whose zoster rash occurs in body areas other than the trunk.

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Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults

Abstract: gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.

Cited by 107 publications

References 21 publications

Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate

Adjuvant and carrier protein-dependent T-cell priming promotes a robust antibody response against the Plasmodium falciparum Pfs25 vaccine candidate

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older

Whence ‘zoster’? The convoluted classical origins of a sometimes illogical term

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