寨卡疫苗研究进展

寨卡病毒系由伊蚊传播的黄病毒,超过20亿人在其流行区域生活。近几年,在中南美洲乃至世界范围内爆发的寨卡疫情已对全球公共卫生事业构成严重威胁。已有研究证实寨卡病毒感染为格林巴利综合征的病因之一;孕妇感染寨卡病毒后,可造成新生儿小头症。早日研制出安全有效的寨卡疫苗之重要性不言而喻。全球率先报道的寨卡疫苗为一款DNA疫苗,其在设计、制备和生产方面均较其他类型疫苗更加简易,且可避免可复制型疫苗因毒力回复而造成对孕妇和胎儿的健康威胁,在寨卡疫苗的研究中具有显著优势。其他传统类型疫苗和基于抗体的新型疫苗等均有研究机构开展研究,并已取得阶段性进展,本文将扼要综述寨卡疫苗的研究现状与进展。     

An assessment of the role of chimpanzees in AIDS vaccine research

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the 'model of choice' in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic responses have been elicited in chimpanzees, via: passive antibody transfer; CD4 analogues; attenuated virus; many types and combinations of recombinant HIV proteins; DNA vaccines; recombinant adenovirus and canarypox vaccines; and many multi-component vaccines using more than one of these approaches. Immunogenicity has also been shown in chimpanzees for vaccinia-based and peptide vaccines. Protection and/or significant therapeutic effects have not been demonstrated by any vaccine to date in humans. Vaccine responses in chimpanzees and humans are highly discordant. Claims of the importance of chimpanzees in AIDS vaccine development are without foundation, and a return to the use of chimpanzees in AIDS research/vaccine development is scientifically unjustifiable.     

间日疟原虫传播阻断疫苗研究新进展

间日疟原虫是导致人类感染疟疾的4种疟原虫之一。由于间日疟具有较强的遗传多样性和更易复发等特点,间日疟原虫的防治得到人们的日益关注,其中疫苗的研发是重要的防控手段,传播阻断疫苗作为可以阻断传播的疫苗,相关方面的研究却刚刚起步。综述了间日疟传播阻断疫苗研究方面的新进展,旨在为间日疟疫苗的研制提供参考。     

Recent Advances in Design and Synthesis of Self-Adjuvanting Lipopeptide Vaccines

Synthetic lipopeptide vaccines are being increasingly investigated mainly because of the advantages they offer over traditional vaccines, including safety of use in humans, high specificity in eliciting immune responses, greater purity and large scale/cost-effective production capacity. Moreover, a number of lipopeptide vaccines designed to possess self-adjuvanting properties have been developed and tested in vitro and in vivo. Producing high levels of serum-specific antibodies against incorporated peptide epitopes, they are showing their potential as effective vaccine candidates without the need for a co-administered adjuvant and/or carrier protein, often associated with undesirable effects in humans. This review presents recent insights on lipopeptide vaccine research and development, particularly on (1) the influence of the orientation of peptide epitopes and lipids on immune responses, (2) the use of carbohydrates for vaccine targeting, adjuvanting or as peptide epitope carriers, and (3) synthetic approaches to highly pure, multi-epitopic vaccine molecules using native chemical ligation techniques. Incorporation of different types of antigens within the same lipopeptide construct could provide a lipopeptide vaccine candidate suitable for safe and effective mucosal administration, which is a comfortable way of drug delivery.     

Characterization of the <Emphasis Type="Italic">ompL1</Emphasis> gene of pathogenic <Emphasis Type="Italic">Leptospira species</Emphasis> in China and cross-immunogenicity of the OmpL1 protein

Background  

The usefulness of available vaccine and serological tests for leptospirosis is limited by the low cross-reactivity of antigens from numerous serovars of pathogenic Leptospira spp. Identification of genus-specific protein antigens (GP-Ag) of Leptospira would be important for development of universal vaccines and serodiagnostic methods. OmpL1, a transmembrane porin of pathogenic leptospires, was identified as a possible GP-Ag, but its sequence diversity and immune cross-reactivity among different serovars of pathogenic leptospires remains largely unknown.     

肺炎链球菌糖疫苗的研究进展

肺炎链球菌(Streptococcus pneumoniae)是引起多种疾病的主要病原体,包括侵袭性感染(如败血症和脑膜炎菌血症),以及更常见的粘膜部位感染(如肺炎、中耳炎和鼻窦炎).根据肺炎链球菌表面荚膜多糖结构的不同可以分成不同的血清型,至今已经鉴定出98种,其中有20种具有高毒力.为了预防肺炎链球菌感染,已研制出...     

Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.     

Are Anti-Phosphoupid Antibodies to be Expected after Proteoliposomal Hepatitis A Vaccination?

Abstract

Introduction

The so-called IRIV- (Immunopotentiating Reconstituted Influenza Virosomes) system (1) is a new type of vaccine. During the past five years extensive experience has been accumulated concerning the immunological and side effects in organisms, both animals and humans, in order to draw up an assessment of the new vaccine Although IRIV could be placed in the category of liposomal vaccines this classification is, however, not quite correct. Such a classification could raise certain questions regarding its use in human medicine. These questions are derived from toxicological studies in animals to which liposomes combined with lipid A were administered It would be valuable to clear up the difference between an IRIV and a liposomal vaccine, with and without lipid A The IRIV is made up of a combination of liposomes (without lipid A) and influenza vims envelopes. Above all, the inclusion of liposomes imposes itself since they already receive much consideration as a new immunological adjuvant and will probably, in the near future, find a large place both as vaccines and as therapeutics.     

Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus

The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.     

Advances in the development of Salmonella-based vaccine strategies for protection against Salmonellosis in humans

Salmonella spp. are important human pathogens globally causing millions of cases of typhoid fever and non-typhoidal salmonellosis annually. There are only a few vaccines licensed for use in humans which all target Salmonella enterica serovar Typhi. Vaccine development is hampered by antigenic diversity between the thousands of serovars capable of causing infection in humans. However, a number of attenuated candidate vaccine strains are currently being developed. As facultative intracellular pathogens with multiple systems for transporting effector proteins to host cells, attenuated Salmonella strains can also serve as ideal tools for the delivery of foreign antigens to create multivalent live carrier vaccines for simultaneous immunization against several unrelated pathogens. Further, the ease with which Salmonella can be genetically modified and the extensive knowledge of the virulence mechanisms of this pathogen means that this bacterium has often served as a model organism to test new approaches. In this review we focus on (1) recent advances in live attenuated Salmonella vaccine development, (2) improvements in expression of foreign antigens in carrier vaccines and (3) adaptation of attenuated strains as sources of purified antigens and vesicles that can be used for subunit and conjugate vaccines or together with attenuated vaccine strains in heterologous prime-boosting immunization strategies. These advances have led to the development of new vaccines against Salmonella which have or will soon be tested in clinical trials.     

Evaluating a Parainfluenza Virus 5-Based Vaccine in a Host with Pre-Existing Immunity against Parainfluenza Virus 5

Parainfluenza virus 5 (PIV5), formerly known as simian virus 5 (SV5), is a paramyxovirus often referred to as canine parainfluenza virus (CPI) in the veterinary field. PIV5 is thought to be a contributing factor to kennel cough. Kennel cough vaccines containing live PIV5 have been used in dogs for many decades. PIV5 is not known to cause any diseases in humans or other animals. PIV5 has been used as a vector for vaccine development for humans and animals. One critical question concerning the use of PIV5 as a vector is whether prior exposure to PIV5 would prevent the use of PIV5-based vaccines. In this work, we have examined immunogenicity of a recombinant PIV5 expressing hemagglutinin (HA) of influenza A virus subtype 3 (rPIV5-H3) in dogs that were immunized against PIV5. We found that vaccination of the dogs containing neutralizing antibodies against PIV5 with rPIV5-H3 generated immunity against influenza A virus, indicting that PIV5-based vaccine is immunogenic in dogs with prior exposure. Furthermore, we have examined exposure of PIV5 in human populations. We have detected neutralizing antibody (nAb) against PIV5 in 13 out of 45 human serum samples (about 29 percent). The nAb titers in humans were lower than that in vaccinated dogs, suggesting that nAb in humans is unlikely to prevent PIV5 from being an efficacious vector in humans.     

Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum with adjuvant saponin protects mice against highly pathogenic avian influenza A virus infection

Pandemics in poultry caused by the highly pathogenic avian influenza (HPAI) A virus occur too frequently globally, and there is growing concern about the HPAI A virus due to the possibility of a pandemic among humans. Thus, it is important to develop a vaccine against HPAI suitable for both humans and animals. Various approaches are underway to develop such vaccines. In particular, an edible vaccine would be a convenient way to vaccinate poultry because of the behaviour of the animals. However, an edible vaccine is still not available. In this study, we developed a strategy of effective vaccination of mice by the oral administration of transgenic Arabidopsis plants (HA‐TG) expressing haemagglutinin (HA) in the endoplasmic reticulum (ER). Expression of HA in the ER resulted in its high‐level accumulation, N‐glycosylation, protection from proteolytic degradation and long‐term stability. Oral administration of HA‐TG with saponin elicited high levels of HA‐specific systemic IgG and mucosal IgA responses in mice, which resulted in protection against a lethal influenza virus infection with attenuated inflammatory symptoms. Based on these results, we propose that oral administration of freeze‐dried leaf powders from transgenic plants expressing HA in the ER together with saponin is an attractive strategy for vaccination against influenza A virus.     

Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus

Background

Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.

Design

Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated IM on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.

Results

All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.

Conclusions

These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.     

候选结核疫苗的评价模型

卡介苗作为目前唯一批准使用的预防结核疫苗,由于无法提供充足的保护力,目前结核病依然是严重危害人类健康的传染病,因此筛选优质候选疫苗迫在眉睫。所有候选疫苗进入临床试验前必须评价其安全性、免疫原性以及有效性。评价结果在一定程度上也预示候选疫苗在人体的免疫作用,也是目前评价候选疫苗是否优于传统卡介苗的依据。论述候选结核疫苗临床试验前所使用的体内和体外评价模型。对评价模型的充分认识将提高候选疫苗评价数据对人体临床试验的预测意义,也可更具体地执行实验动物的替代、减少和优化原则。     

Field studies of cytotoxic T lymphocytes in malaria infections: implications for malaria vaccine development

The search for a cytotoxic T lymphocyte (CTL)-inducing malaria vaccine has moved forward from epitope identification to planning stages of safety and immunogenicity trials of candidate vaccines. Development of CTL-inducing vaccine candidates has taken center stage based on the observation that CTL-mediated protection might be the dominant mechanism by which sterile immunity is achieved in irradiated sporozoite immunization experiments in humans and laboratory animals. However, studies in naturally infected individuals living in endemic areas, as reviewed here by Michael Aidoo and Venkatachalam Udhayakumar, have revealed that CTL induction might be influenced by factors such as parasite variants, host genes, other infections and transmission patterns. The influence of these factors on CTL induction has been demonstrated individually and in various combinations in controlled animal experiments. However, in naturally infected humans, they are presented in a complex host-parasite-environment interaction, in a manner that is not easily achieved in laboratory-based experiments. Understanding these interactions is crucial for the development and testing of CTL-inducing vaccines for humans.     

Particulate delivery systems for animal vaccines

The requirements for veterinary vaccines are different to those of human vaccines. Indeed, while more side effects can be tolerated in animals than in humans; there are stricter requirements in terms of cost, ease of delivery (including to wildlife), and a need to develop vaccines in species for which relatively little is known in terms of molecular immunology. By their nature particulate vaccine delivery systems are well suited to address these challenges. Here, we review particulate vaccine delivery systems, ranging from cm-sized long-distance ballistic devices to nano-bead technology for veterinary species and wildlife.     

Brucella melitensis 16MΔhfq attenuation confers protection against wild‐type challenge in BALB/c mice

Brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. Although effective, the current Brucella vaccines (Rev.1 and M5‐90) have several drawbacks. The first involves residual virulence for animals and humans and the second is the inability to differentiate natural infection from that caused by vaccination. Therefore, Brucella melitensis 16M hfq mutant (16MΔhfq) was constructed to overcome these drawbacks. Similarly to Rev.1 and M5‐90, 16MΔhfq reduces survival in macrophages and mice and induces strong protective immunity in BALB/c mice. Moreover, these vaccines elicit anti‐Brucella‐specific IgG1 and IgG2a subtype responses and induce secretion of gamma interferon and interleukin‐4. The Hfq antigen also allows serological differentiation between infected and vaccinated animals. These results show that 16MΔhfq is an ideal live attenuated vaccine candidate against virulent Brucella melitensis 16M infection. It will be further evaluated in sheep.     

Schistosomiasis vaccine development — the current picture

Development of a vaccine for schistosomiasis, a parasitic disease currently affecting over 200 million people worldwide, has been targeted as a priority by the World Health Organisation. Research demonstrating the ability of humans to acquire natural immunity to schistosome infection, together with the successful use of attenuated vaccines in animals both under laboratory and field conditions, suggest that development of a human vaccine is feasible. Attenuated vaccines for schistosomiasis are considered neither safe nor practicable for human use, however, and therefore other approaches must be considered. This review examines progress currently being undertaken in a number of different areas towards achieving the goal of a safe and effective human vaccine for schistosomiasis.     

Tularemia vaccine: past,present and future

Francisella tularensis is a Gram negative intracellular pathogen that causes the highly debilitating or fatal disease tularemia. F. tularensis can infect a wide range of animals and can be transmitted to humans in a variety of ways, the most common being by the bite of an infected insect or arthropod vector. The attenuated F. tularensis live vaccine strain (LVS) has been used previously under investigational new drug status to vaccinate at-risk individuals. However the history of the strain and lack of knowledge regarding the basis of attenuation has so far prevented its licensing. Therefore the focus of current research is on producing a new vaccine against tularemia that would be suitable for licensing.