Cytokine-adjuvanted HIV-DNA vaccination strategies

This review highlights some of the most common cytokines currently being tested as adjuvants in HIV-1-DNA vaccine regimens. We discuss their use in both the prophylactic and therapeutic setting. Finally, we describe a novel dendritic cell-targeted vaccine candidate for HIV-1 treatment and prevention called DermaVir and explore the combination of the DermaVir technology with the cytokine adjuvants interleukin-7 and interleukin-15.     

New and emerging vaccination strategies for prevention and treatment of dermatological diseases

Accelerated by the rapid advancements of our understanding of the molecular and cellular pathology of diseases and of the components and mechanisms of cellular and humoral immune responses, new vaccination strategies are being developed and explored for treatment and prevention of infectious diseases, cancer, autoimmune disorders and allergies. Many newly developed vaccination strategies are already in clinical trials, some with very promising results. Although most of these strategies are still at very early stages of their development, it is foreseeable that vaccination will evolve to play an important role in prevention, treatment and management of all the above classes of diseases.     

Measles vaccination: new strategies and formulations

Measles is a highly contagious viral disease. With 1 million deaths reported in 1996, measles was the leading cause of vaccine-preventable deaths. However, in recent years, significant progress has been made in measles control, reducing deaths attributed to measles to 454,000 in 2004 and 242,000 in 2006. The main strategy behind this reduction has been the improvement of vaccination coverage and implementation of a second opportunity for immunization with the live-attenuated measles vaccine. The Measles Initiative, a partnership between the American Red Cross, CDC, UNICEF, WHO and UN Foundation, has had a significant role in this achievement. Here, we provide an overview of old and new vaccination strategies, and discuss changes in the route of administration of the existing live-attenuated vaccine, the development of new-generation nonreplicating measles virus vaccine candidates and attempts to use recombinant measles virus as a vector for vaccination against other pathogens.     

Natural HPV immunity and vaccination strategies.

BACKGROUND: the task of preventing premature death in women may be delivered by vaccinating against the high-risk papillomaviruses associated with various malignancies. OBJECTIVES: we will discuss the immune mechanisms likely to be relevant to the control of an HPV infection in the cervix and assess the limited evidence for such immune recognition in the natural history of infection. CONCLUSION: the next generation of vaccination strategies should include the use of HPV 16 early (E2 and/or E6 and/or E7) and late gene targets (L1 and L2) expressed as VLPs with their clinical and immunological evaluation aimed at therapy as well as prophylaxis. Important clinical efficacy assessment may be deliverable in relatively short-term studies by targeting patients with HPV 16 associated vulval intraepithelial neoplasia.     

Tumour immunology,vaccination and escape strategies

Our increasing knowledge of the mechanisms by which tumour cells escape immune effector cells is helping to establish new approaches to therapeutic vaccination against tumour development. One of the escape mechanisms used by tumour cells is the generation of multiple variants with different HLA phenotypes. These MHC class I phenotypic alterations play a key role in the tumour–host scenario, as they are crucial molecules for antigen presentation to T cells and modulation of natural killer (NK) cell activity. This review presents evidence indicating that tumours develop sophisticated MHC phenotypes that allow them to escape immune surveillance. We evaluate the importance of these alterations in terms of the potential development of therapeutic approaches to immune vaccination.     

Novel vaccination strategies and approaches against human tuberculosis

Tuberculosis (TB) remains one of a major health problem worldwide. Tuberculosis vaccine research has made an extraordinary progress over the past few years. However, there is still no replacement for the Bacillus Calmette‐Guérin vaccine, the only TB vaccine licensed for human use. Therefore, the discovery and development of new TB vaccines remains a priority. This article discusses current strategies used to diversify TB vaccines and includes discussion of the status of efforts to improve protection against Mycobacterium tuberculosis (M tb) infection or TB disease by developing new and safe TB vaccines. This article also highlights the current research efforts in immune‐enhancing approaches to improve vaccination efficacy. The development of more effective TB vaccines might have significant impact on global TB control.     

Tumour immunology, vaccination and escape strategies.

Our increasing knowledge of the mechanisms by which tumour cells escape immune effector cells is helping to establish new approaches to therapeutic vaccination against tumour development. One of the escape mechanisms used by tumour cells is the generation of multiple variants with different HLA phenotypes. These MHC class I phenotypic alterations play a key role in the tumour-host scenario, as they are crucial molecules for antigen presentation to T cells and modulation of natural killer (NK) cell activity. This review presents evidence indicating that tumours develop sophisticated MHC phenotypes that allow them to escape immune surveillance. We evaluate the importance of these alterations in terms of the potential development of therapeutic approaches to immune vaccination.     

Influenza vaccination strategies targeting the hemagglutinin stem region

Influenza is one of the best examples of highly mutable viruses that are able to escape immune surveillance. Indeed, in response to influenza seasonal infection or vaccination, the majority of the induced antibodies are strain-specific. Current vaccine against the seasonal strains with the strategy of surveillance-prediction-vaccine does not cover an unmet virus strain leading to pandemic. Recently, antibodies targeting conserved epitopes on the hemagglutinin (HA) protein have been identified, albeit rarely, and they often showed broad protection. These antibody discoveries have brought the feasibility to develop a universal vaccine. Most of these antibodies bind the HA stem domain and accumulate in the memory B cell compartment. Broadly reactive stem-biased memory responses were induced by infection with antigenically divergent influenza strains and were able to eradicate these viruses, together indicating the importance of generating memory B cells expressing high-quality anti-stem antibodies. Here, we emphasize recent progress in our understanding of how such memory B cells can be generated and discuss how these advances may be relevant to the quest for a universal influenza vaccine.     

Prevention strategies: experience of varicella vaccination programmes

Widespread immunization programmes have had a dramatic effect on the morbidity associated with varicella in the USA; mortality has declined by 66% (from 0.41 to 0.14 deaths / million population) and the reduction in hospitalizations is at least 4-fold (from 2.7 to 0.6/100,000 population) compared with the pre-vaccination era. Although varicella outbreaks have occurred in vaccination areas, these data may underestimate the true efficacy of the varicella vaccine, and there is still the potential for two-dose programmes, which have not yet been fully explored in the USA or Canada. Catch-up vaccination programmes have also been regarded as an important approach in susceptible individuals, including women of childbearing potential. Periodic exposure (boosts) to vaccines may potentially help prevent the reactivation of herpes zoster and accumulation of susceptibility in these at-risk groups. Pregnant women may also benefit from prophylaxis with varicella zoster immunoglobulin (VZIG) or possibly with aciclovir. Ongoing surveillance for the reactivation of herpes zoster and safety programmes are also highlighted as key recommendations.     

Design and evaluation of antigen-specific vaccination strategies against cancer

After studies in preclinical mouse models, the efficacy and safety of tumor-specific vaccination strategies is currently being evaluated in cancer patients. The first wave of clinical trials has shown that in general such vaccination strategies are safe. However examples of clinical responses, especially in conjunction with vaccine-induced immune responses, are still scarce. The fact that most trials have so far been performed with end-stage cancer patients can largely account for this deficit. Greater efficacy of anticancer vaccines is expected in patients with less-progressed disease. In addition, the detection of both natural and vaccine-induced T cell immunity needs further improvement.     

结核病疫苗研制的免疫优化策略及新疫苗研究进展

一、卡介苗的计划免疫及其失效原因分析 目前,预防结核病(tuberculosis,TB)惟一有效的疫苗是卡介苗(bacillus calmette-guerin,BCG),一种活的减毒牛型分枝杆菌(M.bovis).由于其良好的安全性以及对儿童重症结核病如粟粒性结核和结核性脑膜炎的显著免疫保护效果,WHO坚持建议在新生儿中接种卡介苗.自1928年以来,BCG至今已在182个国家,对40多亿的儿童进行了接种.根据WHO扩大计划免疫的要求,现在每年仍有1亿多的新生儿接种卡介苗,是目前全球接种最广泛的疫苗之一.然而,BCG对于成人肺结核的保护效果并不理想,大量的临床试验结果显示其免疫保护力介于0～ 80％之间,差异性极大[1].     

Processing and presentation of tumor antigens and vaccination strategies

Various new aspects of antigen processing have been uncovered through the study of tumor antigens. One of these is the production of antigenic peptides by splicing of two distinct peptide fragments. In one of the two cases reported, the proteasome was found to be responsible for splicing. The presentation of another peptide on major histocompatibility complex class I molecules was found to depend on secretion and reuptake of the parent protein, implying a cross-presentation pathway in melanoma cells. Class II presentation of peptides derived from cytosolic proteins now appears to result from autophagy. Based on increased knowledge on antigen processing and presentation, new vaccination strategies are aimed at improving the targeting of antigens to dendritic cells, promoting cross-priming (for example, using chloroquine), improving peptide binding to class I molecules and targeting antigens to both the class I and the class II pathways.     

Therapeutic human papillomavirus DNA vaccination strategies to control cervical cancer

A persistent human papillomavirus (HPV) infection is considered causal and necessary for the continued growth of cervical cancer. Thus, vaccination against HPV represents a plausible approach to prevent and treat cervical cancer. A report in the current issue of the European Journal of Immunology describes a therapeutic HPV DNA vaccination strategy using the HPV-16 E7 antigen fused to the invariant chain to enhance the E7-specific CD8+ and CD4+ T cell immune responses, resulting in a potent anti-tumor effect against E7-expressing tumors. Continued exploration of HPV therapeutic DNA vaccines may lead to eventual clinical application.     

Safety of varicella vaccination strategies: An overview of reviews

The safety of new vaccines under development as well as existing vaccines is a key priority for national and international public health agencies. A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of the number of doses, type of vaccine(s) recommended, age at vaccination and interval between doses for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the safety of varicella vaccination strategies. The review was restricted to immunocompetent children aged 9 months to 6 years inclusive. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. Overlap of included reviews was also assessed. A total of 17 reviews, incorporating both the monovalent varicella only and quadrivalent measles-mumps-rubella-varicella (MMRV) vaccines were included in the overview; six assessed the safety of one-dose strategies, four assessed the safety of two-dose strategies and 14 reviews did not specify the dosing strategy. The evidence suggests that mild local and systemic reactions are relatively common with varicella vaccination. Febrile seizures are also possible adverse effects of both the monovalent and quadrivalent MMRV vaccine, but serious adverse reactions are rare. While most reviews contained methodological flaws, and analysis by vaccine type and dosing strategy was restricted due to lack of detail in reporting of the reviews, there was clear and consistent evidence from a substantial evidence base, comprising 34 randomised controlled trials and 62 other primary studies/reviews, that varicella vaccination is safe.     

Future vaccination strategies against tuberculosis: thinking outside the box

With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future.     

Harnessing CD1d-restricted iNKT cells to design novel vaccination strategies

The success of vaccination strategies depends on the efficient generation of appropriate antigen-specific T- and B-cell responses. The unique position of invariant natural killer T (iNKT) cells at the interface of the innate and adaptive immune systems and their ability to direct the maturation of dendritic cells and B cells offer the possibility of harnessing them to ‘jump-start’ the antigen-specific immune response to both microbial pathogen and tumour antigens. In this brief review, the biology and activation of iNKT cells is discussed, with particular emphasis on the development of pharmacological agents to be used as adjuvants to antigenic proteins, to achieve an iNKT cell-dependent augmentation of antigen-specific T- and B-cell responses. In addition, we discuss the future directions and challenges in translating these findings from experimental data obtained in mice to use in the clinic.     

Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity

Summary: In this article, we describe several novel genetic vaccination strategies designed to facilitate the development of different types of immune responses. These include: the consecutive use of DNA and fowlpoxvirus vectors in "prime-boost" strategies which induce greatly enhanced and sustained levels of both cell-mediated immunity and humoral immunity, including mucosal responses; ii) the co-expression of genes encoding cytokines and cell-surface receptors, and the use of immunogenic carrier molecules, for immune modulation and/or Improved targeting of vector-expressed vaccine antigens; acid iii) the expression of minimal immunogenic arnino acid sequences, particularly cytotoxic CD8+ T-cell determinants, in "polytope" vector vaccines. The capacity to modulate and enhance specific immune responses by the use of approaches such as these may underpin the development of vaccines against diseases for which no effective strategies are currently available.