Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant zoster vaccine:a pooled post-hoc analysis of two parallel randomized trials

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ). Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment. At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4–97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3–99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant. As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment

Effectiveness and impact of the 10-valent pneumococcal conjugate vaccine, PHiD-CV: review of clinical trials and post-marketing experience

Introduction: Pneumococcal diseases (including septicemia, meningitis, pneumonia, and upper respiratory infections) constitute a major public health problem. The World Health Organization recommends pneumococcal conjugate vaccine immunization of young children worldwide. Areas covered: We reviewed evidence on the effects of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), which is used in childhood immunization programs in over 45 countries or regions. The effectiveness of PHiD-CV against invasive pneumococcal disease (IPD), pneumonia, and acute otitis media was assessed. We also present its effect on pneumococcal nasopharyngeal carriage (NPC) and indirect effects (herd protection) among unvaccinated individuals. Expert commentary: Results from randomized, double-blind trials and post-marketing studies in various countries provide evidence of the protective efficacy, effectiveness, and impact of PHiD-CV against pneumococcal diseases. Data from different geographic locations also show reductions in NPC of vaccine pneumococcal serotypes, laying the foundation for indirect protection against pneumococcal disease. In countries where PHiD-CV is included in childhood immunization programs, there are signs of herd protection for vaccine serotypes among unvaccinated individuals. Although increases in non-vaccine serotype IPD and NPC rates were observed, there was an overall reduction of pneumococcal disease.</p

Assessment of the potential public health impact of Herpes Zoster vaccination in Germany

The aim of this study was to compare the public health impact of introducing 2 Herpes Zoster (HZ) vaccines, Zoster Vaccine Live (ZVL) versus a non-live adjuvanted subunit candidate vaccine (HZ/su), in the German population aged 50+ years split into 3 age cohorts, i.e. 50–59, 60–69 and 70+ years, respectively. A multi-cohort static Markov model was developed following age cohorts over their lifetime. Demographic data were obtained from the German federal statistical office. HZ incidence and the proportion of HZ individuals developing post-herpetic neuralgia (PHN) were derived from German specific sources. Age-specific vaccine efficacy and waning rates were based on published clinical trial data. Vaccine coverage for both vaccines was assumed to be 40%, with compliance of the second dose of the HZ/su vaccine of 70%. Sensitivity analyses were performed to assess the robustness of the results. It was estimated that, over the remaining lifetime since vaccination, the HZ/su vaccine would reduce the number of HZ cases by 725,233, 533,162 and 486,794 in the 3 age cohorts, respectively, compared with 198,477, 196,000 and 104,640, using ZVL. The number needed to vaccinate (NNV) to prevent one HZ case ranged from 8 to 11 using the HZ/su vaccine compared with 20 to 50 using ZVL. Corresponding NNV to prevent one PHN case ranged from 39 to 53 using the HZ/su vaccine compared with 94 to 198 using ZVL. Due to the higher, sustained vaccine efficacy, the candidate HZ/su vaccine demonstrated superior public health impact compared with ZVL

Fighting against a protean enemy: immunosenescence, vaccines, and healthy aging

Abstract The progressive increase of the aged population worldwide mandates new strategies to ensure sustained health and well-being with age. The development of better and/or new vaccines against pathogens that affect older adults is one pivotal intervention in approaching this goal. However, the functional decline of various physiological systems, including the immune system, requires novel approaches to counteract immunosenescence. Although important progress has been made in understanding the mechanisms underlying the age-related decline of the immune response to infections and vaccinations, knowledge gaps remain, both in the areas of basic and translational research. In particular, it will be important to better understand how environmental factors, such as diet, physical activity, co-morbidities, and pharmacological treatments, delay or contribute to the decline of the capability of the aging immune system to appropriately respond to infectious diseases and vaccination. Recent findings suggest that successful approaches specifically targeted to the older population can be developed, such as the high-dose and adjuvanted vaccines against seasonal influenza, the adjuvanted subunit vaccine against herpes zoster, as well as experimental interventions with immune-potentiators or immunostimulants. Learning from these first successes may pave the way to developing novel and improved vaccines for the older adults and immunocompromised. With an integrated, holistic vaccination strategy, society will offer the opportunity for an improved quality of life to the segment of the population that is going to increase most significantly in numbers and proportion over future decades

Immunogenicity of the adjuvanted recombinant zoster vaccine : persistence and anamnestic response to additional doses administered 10 years after primary vaccination.

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years (Y) of age (YOA). We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule by following-up adults vaccinated at ≥60 YOA and by modeling, and (2) immunogenicity of 2 additional doses administered 10Y post-initial vaccination. METHODS: Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10Y post-initial vaccination, and modeled through 20Y using a Piecewise, Power law and Fraser model. Immunogenicity and safety of 2 additional RZV doses were also evaluated (NCT02735915). RESULTS: Seventy adults were enrolled. Ten years post-initial vaccination, humoral and CMI responses were ~6-fold and ~3.5-fold above pre-initial vaccination levels, respectively. Predicted immune persistence through 20Y post-initial vaccination was similar across the 3 models. Sixty-two participants (82.6±4.4 YOA) received at least 1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose. CONCLUSIONS: Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10Y after the initial 2-dose course

In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression.

Via a transcription factor, Foxp3, immunoregulatory CD4(+)CD25(+) T cells (T reg cells) play an important role in suppressing the function of other T cells. Adoptively transferring high numbers of T reg cells can reduce the intensity of the immune response, thereby providing an attractive prospect for inducing tolerance. Extending our previous findings, we describe an in vivo approach for inducing rapid expansion of T reg cells by injecting mice with interleukin (IL)-2 mixed with a particular IL-2 monoclonal antibody (mAb). Injection of these IL-2-IL-2 mAb complexes for a short period of 3 d induces a marked (&gt;10-fold) increase in T reg cell numbers in many organs, including the liver and gut as well as the spleen and lymph nodes, and a modest increase in the thymus. The expanded T reg cells survive for 1-2 wk and are highly activated and display superior suppressive function. Pretreating with the IL-2-IL-2 mAb complexes renders the mice resistant to induction of experimental autoimmune encephalomyelitis; combined with rapamycin, the complexes can also be used to treat ongoing disease. In addition, pretreating mice with the complexes induces tolerance to fully major histocompatibility complex-incompatible pancreatic islets in the absence of immunosuppression. Tolerance is robust and the majority of grafts are accepted indefinitely. The approach described for T reg cell expansion has clinical potential for treating autoimmune disease and promoting organ transplantation