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

ABSTRACT: 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 socio-economic 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 live-attenuated 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.

SUBMITTER: Wagner A

PROVIDER: S-EPMC7190794 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Wagner Angelika A Weinberger Birgit B

Frontiers in immunology 20200423

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 socio-economic 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 decreas ...[more]

PMID: 32391017

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Project description:Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette-Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer. Data supporting a cancer therapeutic use was found for 16 vaccines. For 10 (BCG, diphtheria, tetanus, human papillomavirus, influenza, measles, pneumococcus, smallpox, typhoid and varicella-zoster), clinical trials have been conducted or are ongoing. Within the remaining 6, preclinical evidence supports further evaluation of the rotavirus, yellow fever and pertussis vaccine in carefully designed clinical trials. The mechanistic evidence for the cholera vaccine, combined with the observational data in colorectal cancer, is also supportive of clinical translation. There is limited data for the hepatitis B and mumps vaccine (without measles vaccine). Four findings are worth highlighting: the superiority of intravesical typhoid vaccine instillations over BCG in a preclinical bladder cancer model, which is now the subject of a phase I trial; the perioperative use of the influenza vaccine to limit and prevent the natural killer cell dysfunction induced by cancer surgery; objective responses following intratumoral injections of measles vaccine in cutaneous T-cell lymphoma; objective responses induced by human papillomavirus vaccine in cutaneous squamous cell carcinoma. All vaccines are intended to induce or improve an anti-tumor (immune) response. In addition to the biological and immunological mechanisms that vary between vaccines, the mode of administration and sequence with other (immuno-)therapies warrant more attention in future research.

Project description:Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. STATEMENT OF SIGNIFICANCE: This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development.

Dataset Information

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

Publications

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

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