Vaccine safety evaluation: Practical aspects in assessing benefits and risks

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Vaccination programs for older adults in an era of demographic change

Objectives Populations are aging worldwide. This paper summarizes some of the challenges and opportunities due to the increasing burden of infectious diseases in an aging population. Results Older adults typically suffer elevated morbidity from infectious disease, leading to increased demand for healthcare resources and higher healthcare costs. Preventive medicine, including vaccination can potentially play a major role in preserving the health and independence of older adults. However, this potential of widespread vaccination is rarely realized. Here, we give a brief overview of the problem, discuss concrete obstacles and the potential for expanded vaccination programs to promote healthy aging. Conclusion The increasing healthcare burden of infectious diseases expected in aging populations could, to a large extent, be reduced by achieving higher vaccination coverage among older adults. Vaccination can thus contribute to healthy aging, alongside healthy diet and physical exercise. The available evidence indicates that dedicated programs can achieve substantial improvements in vaccination coverage among older adults, but more research is required to assess the generalizability of the results achieved by specific interventions (see Additional file 1)

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

From discovery to licensure, the Adjuvant System story

Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines

Health care professionals’ perspectives on life-course immunization: A qualitative survey from a european conference

Today, fewer children die each year from vaccine-preventable diseases than older adults. Health systems need new immunization strategies to tackle the burden of vaccine-preventable disease in an aging society. Alife-course immunization (LCI) approach—which entails vaccination throughout an individual’s lifespan—enables adults to age with reduced risk to disease, thereby enabling healthy, active and productive aging. We conducted an audience response system (ARS)-based survey to investigate HCPperspectives on LCI in an opportunistic sample of 222 health care professionals (HCPs) from around the world who attended a European infectious diseases conference. Survey results show that LCI is a priority for HCPs (77.4%–88.6%), with most of them stating the need to frame it as a part of a healthy lifestyle (91.0%–100.0%). Insu cient LCI recommendations by vaccine providers (12.9%–33.3%) and governments (15.2%–41.9%) and insu cient targeted budget allocation (6.1%–21.7%) were indicated as the main barriers to implement LCI, ahead of vaccine hesitancy (9.7%–15.2%). HCPs were willing to make LCI a gateway to healthy aging but need support to work together with other stakeholders involved in the vaccination journey. This could be a step towards equitable health care for all of society

Correction to: Vaccine Hesitancy as a Challenge or Vaccine Confidence as an Opportunity for Childhood Immunisation in India

In the original publication, the fourth author name was incorrectly published as Jayant Ray

Vaccine Adjuvants: from 1920 to 2015 and Beyond

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines

The need for vaccination in adults with chronic (noncommunicable) diseases in India – lessons from around the world

Worldwide, chronic diseases (noncommunicable diseases [NCDs]) cause 41 million (71%) deaths annually. They are the leading cause of mortality in India, contributing to 60% of total deaths each year. Individuals with these diseases are more susceptible to vaccine-preventable diseases (VPDs) and have an increased risk of associated disease severity and complications. This poses a substantial burden on healthcare systems and economies, exemplified by the COVID-19 pandemic. Vaccines are an effective strategy to combat these challenges; however, utilization rates are inadequate. With India running one of the world’s largest COVID-19 vaccination programs, this presents an opportunity to improve vaccination coverage for all VPDs. Here we discuss the burden of VPDs in those with NCDs, the benefit of vaccinations, current challenges and possible strategies that may facilitate implementation and accessibility of vaccination programs. Effective vaccination will have a significant impact on the disease burden of both VPDs and NCDs and beyond

Life-course immunization as a gateway to health

Introduction: Extending the benefits of vaccination against infectious diseases from childhood throughout the entire life-span is becoming an increasingly urgent priority in view of the world’s aging population, emergence and reemergence of infectious diseases, and the necessity to invest more on prevention versus cure in global healthcare. Areas covered: This perspective discusses how life-course immunization could benefit human health at all stages of life. To achieve this, the current vaccination paradigm should be changed and all stakeholders have a role to play. Expert commentary: To enhance immunization confidence in the population, it is essential that stakeholders eliminate complacency toward infectious diseases, improve vaccination convenience, remove barriers among different healthcare specialties, and address prevention as a single entity. They must also consider societal and cultural mindsets by understanding and including public viewpoints. A new “4Cs’ model encompassing convenience, confidence, complacency, and cultural acceptance is proposed to convert ‘vaccine availability’ to ‘vaccination acceptance’ throughout life. Life-course vaccination should become the new social norm of a healthy life-style, along with a healthy diet, adequate physical exercise, and not smoking. We are ‘all in’ to make life-course immunization a gateway for all people to lead longer, healthier lives