预防接种知情告知专家共识(下)

《中华人民共和国疫苗管理法》和其他相关法律法规对受种者或其监护人的疫苗和预防接种工作知情提出了要求,对预防接种告知方式和内容作出了规定.本共识以该法和《预防接种工作规范》为基础,借鉴国内外经验,阐述了预防接种知情告知的发展和形式,制定了预防接种知情告知理论框架、标准流程和信息、非免疫规划疫苗知情告知原则以及各疫苗知情同...     

CD4+ T cells in antitumor immunity: utility of an Ii-Key HER2/neu hybrid peptide vaccine (AE37)

Background: Early clinical trials of HER2/neu-derived peptide vaccines indicate that they may be useful for preventing recurrence in breast cancer patients rendered disease-free after standard-of-care therapy. An effective vaccination strategy will probably require stimulation of T helper (Th) cells. AE37 is an HER2/neu-derived peptide that has been modified to enhance antigen-specific stimulation of Th cells by linkage of the Ii-Key moiety of the MHC class II-associated invariant chain (Ii protein). Objective: To review the literature regarding the role of a Th response in immunotherapy with a focus on this novel HER2/neu-derived AE37 peptide. Results/conclusion: Improved immuno-genicity of the AE37 Ii-key hybrid peptide has been demonstrated in animal models, ex vivo patient cells, and, most recently, in a Phase I clinical trial in breast cancer patients. Future clinical trials incorporating AE37 into a peptide vaccine strategy are warranted.     

Investigation of Foot and Mouth Disease hotspots in northern Lao PDR

Foot and mouth disease (FMD) is an endemic transboundary disease in the Mekong region, and FMD records of reports to animal health authorities in Lao PDR between 2009 and 2011 were reviewed. FMD outbreaks occurred in 2 of 3 years in eight districts in three of the eight northern Lao PDR provinces, locations suggested as FMD ‘hotspots’. The relatively higher risk of recurrence of FMD in these districts was likely due to the presence of a dense large ruminant population, extensive animal trading including transboundary movements and ineffective animal movement controls. As an understanding of the epidemiology of FMD in these ‘hotspots’ may offer insights into improved FMD control in the region, a study of an outbreak of FMD occurring in early 2010 following failure to vaccinate was conducted in the endemic ‘hotspot’ area of Paek district in Xiengkhoung province where in early 2009, a major outbreak of FMD in the district had been prevented in two villages by vaccination. The 2010 outbreak included collection of tissue samples 1 week after the onset of FMD that confirmed infection with FMD virus serotype O (Myanmar topotype) in a population of 239 large ruminants, comprising 167 cattle and 72 buffalo. A survey by interview of 30 farmers conducted in July 2010 documented high morbidity in cattle and buffalo (>90%) and identified disease risk factors, including increased trading of animals at the end of the rice harvest, plus several failures of biosecurity. In late 2010 and early 2011, a total of 40 and 72 serum samples were collected from large ruminants prior to and post‐FMD vaccination respectively and tested by LPB‐ELISA. Antibodies were present in the pre‐vaccination samples attributable to previous exposure to FMD virus and significantly rising post‐vaccination titres indicated likely temporary protection against future FMDV infection. It was concluded that to provide sufficient control of FMD in this ‘hotspot’, regular vaccination, particularly prior to the peak risk period in December‐February, plus improved farmer knowledge of disease transmission risk and biosecurity, is required. Although low rural education standards and language barriers because of multiple ethnic groups pose a challenge for the successful delivery of extension programmes in northern Lao PDR, training to improve disease recognition and reporting plus village‐level biosecurity practices is considered important in FMD ‘hotspots’ if sustainable regional initiatives directed at FMD control are to be achieved.     

Progress in active-specific immunotherapy of brain malignancies

Despite the significant advances in neurosurgical techniques and oncology treatment regimens, the prognosis of patients with brain malignancies remains dismal. Brain tumours remain as lethal in the beginning of this new millennium as they were 30 years ago. Among the promising treatment modalities being tested are various immunotherapeutic approaches. Development of cancer vaccines, also known as active-specific immunotherapy, for malignant brain tumours is summarised in this review. Understanding the mechanisms behind vaccinations and the initiation of immune response have helped the design and improvement of the efficacy of clinical vaccines. The emergence of the antigen-presenting properties of dendritic cells brings the cancer vaccine field into a new generation. Preclinical work on the use of dendritic cell-based vaccine for malignant brain tumours are encouraging. The move from these preliminary studies to the clinic is anticipated with high hope.     

Cellular and molecular chaperone fusion vaccines: Targeting resistant cancer cell populations

Abstract

Molecular chaperone-based vaccines offer a number of advantages for cancer treatment. We have discussed the deployment of a vaccine prepared by gentle isolation of Hsp70 from tumour dendritic cell fusions (Hsp70 fusion vaccine). The vaccine was highly effective in triggering specific T cell immunity and in the treatment of tumour-bearing mice and the preparation was shown to retain an increased amount of tumour antigens compared to other chaperone-based isolates. This approach has the further advantage that tumour sub-populations could be used to prepare the Hsp70 fusion vaccine. Cellular fusion vaccines were made to specifically target drug-resistant cancer cells and tumour cell populations enriched in ovarian cancer stem cells (CSC). Such vaccines showed enhanced capacity to trigger T cell immunity to these resistant ovarian carcinoma populations. We have discussed the potential of using the cellular and Hsp70 fusion vaccine approaches in therapy of treatment-resistant cancer cells and its deployment in combination with ionising radiation or hyperthermia to enhance the effectiveness of both forms of therapy.     

Novel peptide-based HIV-1 immunotherapy

Therapeutic immunisation of human immunodeficiency virus type 1-infected individuals should be actively pursued in the first instance to augment highly active antiretroviral therapy regimens. Peptide-based immunotherapeutic strategies offer considerable advantages over conventional approaches, particularly regarding safety. Peptide design itself is becoming increasingly sophisticated, with the rapid evolution of bioinformatics tools that can analyse not only T cell epitopes, but also their potential for successful presentation on diverse human leukocyte antigen (HLA) class I or II following intracellular processing by antigen-presenting cells (APCs). By targeting conserved viral domains, peptides acquire improved reactivity to diverse viral strains. Dendritic cells represent a powerful route of administration, as they are the most potent APCs and can present exogenous peptides on both HLA class I and II through the process of cross-presentation. In this way, soluble peptides can thereby stimulate both CD4+ and CD8+ T cells.     

An update on vaccines for tuberculosis – there is more to it than just waning of BCG efficacy with time

Introduction: Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide.

Areas covered: After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials.

Expert opinion: It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.     

Data and product needs for influenza immunization programs in low- and middle-income countries: Rationale and main conclusions of the WHO preferred product characteristics for next-generation influenza vaccines

In 2017, WHO convened a working group of global experts to develop the Preferred Product Characteristics (PPC) for Next-Generation Influenza Vaccines. PPCs are intended to encourage innovation in vaccine development. They describe WHO preferences for parameters of vaccines, in particular their indications, target groups, implementation strategies, and clinical data needed for assessment of safety and efficacy. PPCs are shaped by the global unmet public health need in a priority disease area for which WHO encourages vaccine development. These preferences reflect WHO’s mandate to promote the development of vaccines with high public health impact and suitability in Low- and Middle-Income Countries (LMIC). The target audience is all entities intending to develop or to achieve widespread adoption of a specific influenza vaccine product in these settings. The working group determined that existing influenza vaccines are not well suited for LMIC use. While many developed country manufactures and research funders prioritize influenza vaccine products for use in adults and the elderly, most LMICs do not have sufficiently strong health systems to deliver vaccines to these groups. Policy makers from LMICs are expected to place higher value on vaccines indicated for prevention of severe illness, however the clinical development of influenza vaccines focuses on demonstrating prevention of any influenza illness. Many influenza vaccine products do not meet WHO standards for programmatic suitability of vaccines, which introduces challenges when vaccines are used in low-resource settings. And finally, current vaccines do not integrate well with routine immunization programs in LMICs, given age of vaccine licensure, arbitrary expiration dates timed for temperate country markets, and the need for year-round immunization in countries with prolonged influenza seasonality. While all interested parties should refer to the full PPC document for details, in this article we highlight data needs for new influenza vaccines to better demonstrate the value proposition in LMICs.     

Memory B cell response to a PCV-13 booster in 3.5 year old children primed with either PCV-7 or PCV-13

Pneumococcal protein-polysaccharide conjugate vaccines provide direct protection against Streptococcus pneumoniae through the induction of persistent anti-polysaccharide antibodies, and by priming for a rapid secondary antibody response. Memory B cells (B_MEM) generated during an initial immune response are responsible for both the more rapid and quantitatively greater secondary antibody response and are also thought to contribute to the ongoing production of plasma cells providing long-term antibody persistence. We recruited 3.5-year-old children who had participated in a previous clinical trial comparing infant immunization with either a 7-valent (PCV-7) or a 13-valent pneumococcal conjugate vaccine (PCV-13) to investigate whether prior priming with pneumococcal antigens influences B_MEM responses. Blood was taken before and 1 month after a PCV-13 booster. B_MEM were quantified using a cultured ELISpot assay for pneumococcal serotypes 1, 3, 4, 14, 19A, 23F, and with diphtheria and tetanus toxoid as controls, and then correlated with serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers. In total, blood samples from 62 participants were available for analysis. Serotype-specific B_MEM frequencies were generally low at baseline (before boost) although for serotypes 14 and 3, they were significantly higher in children primed with PCV-13 than PCV-7 primed children. Following the PCV-13 booster, B_MEM frequencies increased and were not different between the groups for all serotypes. A strong inverse correlation was found between antibody concentrations and OPA titers at baseline and B_MEM following booster vaccination for serotype 3 but not for other serotypes suggesting that, for this serotype, pre-existing serotype-specific antibodies may inhibit B_MEM formation in response to vaccination.Clinicaltrials.gov registration number: NCT01095471.     

History of vaccination

Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.