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1.
在流感灭活疫苗中添加佐剂可以提高疫苗的免疫原性,节约抗原用量。一些天然中草药多糖具有潜在的佐剂效应。本文探讨了人参多糖(ginseng polysaccharide,GPS)在新甲型H1N1流感病毒裂解型灭活疫苗中的佐剂效应。将不同剂量GPS与新甲型H1N1流感病毒灭活疫苗混合,共同免疫小鼠一次,通过检测免疫后在小鼠体内诱导产生的疫苗特异性IgM、IgG、IgG1和IgG2a抗体情况来评价GPS作为流感病毒灭活疫苗佐剂的免疫增强效果,并与不添加佐剂的疫苗和加有铝佐剂的疫苗的免疫效果作比较。结果显示,GPS与铝佐剂一样能显著提高和维持疫苗特异性IgG抗体滴度,同时提高IgM抗体水平,其中800μgGPS的佐剂效果最好。因此我们认为GPS可以作为流感病毒灭活疫苗的一种候选佐剂。 相似文献
2.
Effect of apoptosis‐associated speck‐like protein containing a caspase recruitment domain on vaccine efficacy: Overcoming the effects of its deficiency with aluminum hydroxide adjuvant
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Deuk‐Ki Lee Eun‐Young Lee Ryoon‐Ho Kim Hye‐Won Kwak Joo Young Kim Hun Kim Kyung‐Won Kang Sang‐Myeong Lee Jong‐Hwan Park Jun Chang Jae‐Hwan Nam 《Microbiology and immunology》2018,62(3):176-186
3.
《Biologicals》2000,28(2):95-103
Influenza epidemics are an important cause of morbidity and mortality throughout the world. Current recommendations from Health Authorities emphasize annual immunization of people who are particularly at risk from an influenza virus infection; however, vaccination of working adults and of school children also has been shown to provide public health benefits. To give it a more advantageous reactogenicity profile than the diethylether-split influenza vaccines available previously, a split virion influenza vaccine has been produced with TritonX-100. In a series of clinical trials, Aventis Pasteur (formerly, Pasteur Mérieux Connaught) tested both the safety and immunogenicity of this TritonX-100-split virion influenza vaccine in 566 subjects (42 children, 296 adults, and 228 elderly adults) during three influenza seasons (1991, 1993, and 1995). The TritonX-100-split virion vaccine was well tolerated: no serious adverse events were recorded during the 21 days following immunization. Among the local reactions observed, mild pain, redness, or induration at the injection site were the most frequently reported. Fever (38·0 to 38·5°C) was noted in five adults or elderly subjects (1%), and in two children (5%). Immunogenicity was determined by measuring serum haemagglutinin antibody titres specific to each vaccine virus strain. In each of the three vaccination campaigns, the TritonX-100-split virion influenza vaccine fulfilled the Notes for Guidance on Harmonization of Requirements for Influenza Vaccines outlined by the Committee for Proprietary Medicinal Products (CPMP) of the European Community for an influenza virus vaccine (i.e., seroprotection, seroconversion, or increase of geometric mean titre) in all age groups. 相似文献
4.
Immunogenicity and safety of an inactivated quadrivalent influenza vaccine in healthy adults: a phase II,open‐label,uncontrolled trial in Japan
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Yukari Tsurudome Kazuhiko Kimachi Yusuke Okada Kenta Matsuura Yusuke Ooyama Kayo Ibaragi Yoichiro Kino Kohji Ueda 《Microbiology and immunology》2015,59(10):597-604
Two antigenically distinct B strain lineages of influenza virus have co‐circulated since the mid‐1980s; however, inactivated trivalent influenza vaccines contain only one B lineage. The mismatch between the circulating and vaccine lineages has been a worldwide issue. In this study, an inactivated quadrivalent influenza vaccine (QIV) candidate containing two B lineages was manufactured and its immunogenicity and safety evaluated in an open‐label, uncontrolled trial. In this phase II trial, 50 subjects aged 20–64 years received two doses of QIV s.c. 1 to 4 weeks apart. Sera were collected pre‐ and post‐vaccination and safety assessed from the first vaccination to 21 ± 7 days after the second vaccination. After the first vaccination, hemagglutination inhibition titers against each strain increased markedly; the seroconversion rate, geometric mean titer ratio and seroprotection rate being 94.0%, 24.93, and 100.0%, respectively, for the A/H1N1pdm09 strain; 94.0%, 12.47, and 98.0%, respectively, for the A/H3N2 strain; 54.0%, 4.99, and 66.0%, respectively, for B/Yamagata strain, and 72.0%, 6.23 and 80.0%, respectively, for the B/Victoria strain, thus fulfilling the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use. Also, the QIV induced sufficient single radial hemolysis and neutralizing antibodies against all four vaccine strains. No noteworthy adverse events were noted. The results of this trial demonstrate that QIV is well tolerated and immunogenic for each strain, suggesting that QIV potentially improves protection against influenza B by resolving the issue of B lineage mismatch. 相似文献
5.
Influenza A virus is a negative-strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A virus would induce not only highly robust strain-specific humoral and T-cell immune responses but also cross-protective immunity in which an immune response to antigens from a particular viral subtype (e.g., H3N2) would protect against other viral subtypes (e.g., H1N1). Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/noncoding DNA complexes (CLDC) as adjuvant to whole inactivated influenza A virus vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDC-adjuvanted vaccine induced higher total influenza virus-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multicytokine-producing influenza virus-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted vaccine than with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated influenza virus vaccine. 相似文献
6.
Tanja Smith Martha M. O'Kennedy Daniel B.R. Wandrag Modupeore Adeyemi Celia Abolnik 《Plant biotechnology journal》2020,18(2):502-512
The efficacy, safety, speed, scalability and cost‐effectiveness of producing hemagglutinin‐based virus‐like particle (VLP) vaccines in plants are well‐established for human influenza, but untested for the massive poultry influenza vaccine market that remains dominated by traditional egg‐grown oil‐emulsion whole inactivated virus vaccines. For optimal efficacy, a vaccine should be closely antigenically matched to the field strain, requiring that influenza A vaccines be updated regularly. In this study, an H6 subtype VLP transiently expressed in Nicotiana benthamiana was formulated into a vaccine and evaluated for efficacy in chickens against challenge with a heterologous H6N2 virus. A single dose of the plant‐produced H6 VLP vaccine elicited an immune response comparable to two doses of a commercial inactivated H6N2 vaccine, with mean hemagglutination inhibition titres of 9.3 log2 and 8.8 log2, respectively. Compared to the non‐vaccinated control, the H6 VLP vaccine significantly reduced the proportion of shedders and the magnitude of viral shedding by >100‐fold in the oropharynx and >6‐fold in the cloaca, and shortened oropharyngeal viral shedding by at least a week. Despite its potency, the cost of the antigenic mismatch between the inactivated H6N2 vaccine and challenge strain was evident not only in this vaccine's failure to reduce viral shedding compared to the non‐vaccinated group, but its apparent exacerbation of oropharyngeal viral shedding until 21 days post‐challenge. We estimate that a kilogram of plant leaf material can produce H6 VLP vaccines sufficient for between 5000 and 30 000 chickens, depending on the effective dose and whether one or two immunizations are administered. 相似文献
7.
8.
Chompoonuch Sawaengsak Yasuko Mori Koichi Yamanishi Ampol Mitrevej Nuttanan Sinchaipanid 《AAPS PharmSciTech》2014,15(2):317-325
Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripolyphosphate (TPP) at the CS/TPP ratio of 1:0.6 using 2 h mixing time. The CS/TPP nanoparticles were used as delivery vehicle of an intranasal influenza vaccine made of hemagglutinin (HA)-split influenza virus product. Innocuousness, immunogenicity, and protective efficacy of the CS/TPP-HA vaccine were tested in influenza mouse model in comparison with the antigen alone vaccine. The CS/TPP-HA nanoparticles had required characteristics including nano-sizes, positive charges, and high antigen encapsulation efficiency. Mice that received two doses of the CS/TPP-HA vaccine intranasally showed no adverse symptoms indicating the vaccine innocuousness. The animals developed higher systemic and mucosal antibody responses than vaccine made of the HA-split influenza virus alone. The CS/TPP-HA vaccine could induce also a cell-mediated immune response shown as high numbers of IFN-γ-secreting cells in spleens while the HA vaccine alone could not. Besides, the CS nanoparticle encapsulated HA-split vaccine reduced markedly the influenza morbidity and also conferred 100% protective rate to the vaccinated mice against lethal influenza virus challenge. Overall results indicated that the CS nanoparticles invented in this study is an effective and safe delivery vehicle/adjuvant for the influenza vaccine. 相似文献
9.
The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in Nicotiana benthamiana, we have recently demonstrated that a candidate Virus-Like Particle (VLP) vaccine can be generated within 3 weeks of release of sequence information. Herein we report that alum-adjuvanted plant-made VLPs containing the hemagglutinin (HA) protein of H5N1 influenza (A/Indonesia/5/05) can induce cross-reactive antibodies in ferrets. Even low doses of this vaccine prevented pathology and reduced viral loads following heterotypic lethal challenge. We further report on safety and immunogenicity from a Phase I clinical study of the plant-made H5 VLP vaccine in healthy adults 18-60 years of age who received 2 doses 21 days apart of 5, 10 or 20 μg of alum-adjuvanted H5 VLP vaccine or placebo (alum). The vaccine was well tolerated at all doses. Adverse events (AE) were mild-to-moderate and self-limited. Pain at the injection site was the most frequent AE, reported in 70% of vaccinated subjects versus 50% of the placebo recipients. No allergic reactions were reported and the plant-made vaccine did not significantly increase the level of naturally occurring serum antibodies to plant-specific sugar moieties. The immunogenicity of the H5 VLP vaccine was evaluated by Hemagglutination-Inhibition (HI), Single Radial Hemolysis (SRH) and MicroNeutralisation (MN). Results from these three assays were highly correlated and showed similar trends across doses. There was a clear dose-response in all measures of immunogenicity and almost 96% of those in the higher dose groups (2 × 10 or 20 μg) mounted detectable MN responses. Evidence of striking cross-protection in ferrets combined with a good safety profile and promising immunogenicity in humans suggest that plant-based VLP vaccines should be further evaluated for use in pre-pandemic or pandemic situations. TRIAL REGISTRATION: ClinicalTrials.gov NCT00984945. 相似文献
10.
Ming-Hsi Huang Su-Chen Lin Chia-Hsin Hsiao Hsin-Ju Chao Hung-Ren Yang Chien-Chun Liao Po-Wei Chuang Huang-Pi Wu Chiung-Yi Huang Chih-Hsiang Leng Shih-Jen Liu Hsin-Wei Chen Ai-Hsiang Chou Alan Yung-Chih Hu Pele Chong 《PloS one》2010,5(8)
Background
Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.Methodology/Principal Findings
After formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span®85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 µg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs) were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption)-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2).Conclusions/Significance
Encapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a potential shortage of prophylactic vaccines against local infectious diseases, in particular pandemic influenza. Moreover, the cross-clade neutralizing antibody responses data verify the potential of such adjuvanted H5N1 candidate vaccine as an effective tool in pre-pandemic preparedness. 相似文献11.
Hyekwon Kim Jeong-Ki Kim Hohyun Song Jungah Choi Byoungshik Shim Bokyu Kang Hyoungjoon Moon Minjoo Yeom Sang-Hyun Kim Daesub Song Manki Song 《Journal of microbiology (Seoul, Korea)》2014,52(9):794-800
Sublingual (SL) administration of influenza vaccine would be non-invasive and effective way to give human populations protective immunity against the virus, especially when pandemic influenza outbreaks. In this study, the efficacy of pandemic influenza virus-based subunit vaccines was tested after sublingual (SL) adjuvant administration in pigs. Eight specific pathogen-free Yucatan pigs were divided into 4 groups: nonvaccinated but challenged (A) and vaccinated and challenged (B, C, and D). The vaccinated groups were subdivided by vaccine type and inoculation route: SL subunit vaccine (hemagglutinin antigen 1 [HA1] + wild-type cholera toxin [wtCT], B); IM subunit vaccine (HA1 + aluminum hydroxide, C); and IM inactivated vaccine (+ aluminum hydroxide, D). The vaccines were administered twice at a 2-week interval. All pigs were challenged with pandemic influenza virus (A/swine/GCVP-KS01/2009 [H1N1]) and monitored for clinical signs, serology, viral shedding, and histopathology. After vaccination, hemagglutination inhibition titre was higher in group D (320) than in the other vaccinated groups (40–80) at the time of challenge. The mobility and feed intake were reduced in group C. Both viral shedding and histopathological lesions were reduced in groups B and D. Although this study has limitation due to the limited number of pigs (2 pigs per a group), the preliminary data in this study provided the protective potential of SL administration of bacteria-expressed pandemic H1N1 influenza vaccine in pigs. There should be additional animal studies about effective adjuvant system and vaccine types for the use of SL influenza vaccination. 相似文献
12.
Lu Huijun Huo Xiaowei Zhang Ying Zheng Min Ma Mingxiao Zhang Hongyong Jin Minglan Shen Guoshun Jia Leili Ji Yue Li Xu Jin Kuoshi Jin Ningyi 《Microbiology and immunology》2008,52(9):440-446
DNA‐based vaccination is an attractive alternative for overcoming the disadvantages of inactivated virus vaccines; however, DNA vaccines alone often generate only weak immune responses. In this study, the efficacy of LMS as a chemical adjuvant on a DNA vaccine (pVIR‐P12A‐IL18‐3C) encoding the P1‐2A and 3C genes of the FMDV and swine IL‐18, which provides protection against FMDV challenge, was tested. All test pigs were administered booster vaccinations 28 days after the initial inoculation, and were challenged with 1000 ID50 FMDV O/NY00 20 days after the booster vaccination. Positive and negative control groups were inoculated with inactivated virus vaccine and PBS respectively. The DNA vaccine plus LMS induced greater humoral and cell‐mediated responses than the DNA vaccine alone, as evidenced by higher concentrations of neutralizing and specific anti‐FMDV antibodies, and by higher concentrations of T‐lymphocyte proliferation and IFN‐γ production, respectively. FMDV challenge revealed that the DNA vaccine plus LMS provided higher protection than the DNA vaccine alone. This study demonstrates that LMS may be useful as an adjuvant for improving the protective efficiency of DNA vaccination against FMDV in pigs. 相似文献
13.
Production of inactivated influenza H5N1 vaccines from MDCK cells in serum-free medium 总被引:3,自引:0,他引:3
Hu AY Tseng YF Weng TC Liao CC Wu J Chou AH Chao HJ Gu A Chen J Lin SC Hsiao CH Wu SC Chong P 《PloS one》2011,6(1):e14578
Background
Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system.Principal Finding
The current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3×106 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1±0.3×108 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera.Conclusions
The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production. 相似文献14.
Igari H Segawa S Watanabe A Suzuki A Watanabe M Sakurai T Kuroda F Watanabe M Tatsumi K Nakayama M Nakayama T Suzuki K Sato T 《Microbiology and immunology》2010,54(10):618-624
A phase III observational study evaluating a single-dose of an inactivated, split-virus, unadjuvanted AH1pdm vaccine in HCW was conducted. A safe and effective vaccine was needed after the emergence of AH1pdm in April 2009. We analyzed the immunogenicity and safety of the vaccine. A total of 409 subjects were enrolled and given 15 μg hemagglutinin antigen by s.c. injection. Antibody titers were measured using hemagglutination-inhibition antibody assays before vaccination and 28 days after. The co-primary immunogenicity end-points were the proportion of subjects with antibody titers of 1:40 or more, the proportion of subjects with either seroconversion or a significant increase in antibody titer, and the factor increase in geometric mean titer. We collected 389 pair samples. Antibody titers of 1:40 or more were observed in 148 of 389 subjects (38.0%, 95% CI: 33.2-42.9). The immunogenicity was also confirmed in other end-points, but was not sufficient and was lower than in previous reports. A total of 96 of adverse events was reported: 51 local events and 57 systemic events. There were 12 subjects with both local and systemic events. Nearly all events were mild to moderate except in four subjects. A single 15-μg dose of AH1pdm vaccine did not induce sufficient immunogenicity in HCW, with mild-to-moderate vaccine-associated adverse events. We need to consider further improvement of the AH1pdm vaccine program in HCW for the prevention of nosocomial infection, as well as for the benefit of HCW. 相似文献
15.
16.
Heng Liu Harshad P. Patil Jacqueline de Vries-Idema Jan Wilschut Anke Huckriede 《PloS one》2012,7(12)
Identification of safe and effective adjuvants remains an urgent need for the development of inactivated influenza vaccines for mucosal administration. Here, we used a murine challenge model to evaluate the adjuvant activity of GPI-0100, a saponin-derived adjuvant, on influenza subunit vaccine administered via the intranasal or the intrapulmonary route. Balb/c mice were immunized with 1 µg A/PR/8 (H1N1) subunit antigen alone or in combination with varying doses of GPI-0100. The addition of GPI-0100 was required for induction of mucosal and systemic antibody responses to intranasally administered influenza vaccine and significantly enhanced the immunogenicity of vaccine administered via the intrapulmonary route. Remarkably, GPI-0100-adjuvanted influenza vaccine given at a low dose of 2×1 µg either in the nares or directly into the lungs provided complete protection against homologous influenza virus infection. 相似文献
17.
Koblin BA Casapia M Morgan C Qin L Wang ZM Defawe OD Baden L Goepfert P Tomaras GD Montefiori DC McElrath MJ Saavedra L Lau CY Graham BS;NIAID HIV Vaccine Trials Network 《PloS one》2011,6(9):e24517
Background
In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.Methodology/Principal Findings
This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5) vaccine boost given at 6 months by intramuscular (IM), intradermal (ID), or subcutaneous (SC) route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18–50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20). After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS) at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.)Conclusions/Significance
This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.Trial Registration
ClinicalTrials.gov NCT00384787相似文献18.
While studying the haemagglutinin content of whole virus inactivated influenza vaccines by the single radial diffusion test and quantitative electron microscopy, it was found that not all haemagglutinin measured by single radial diffusion was bound to virions, a part of it being in a free state. The influence of unbound haemagglutinin on the immunogenicity of whole virus inactivated influenza vaccine is discussed. In addition, the use of single radial diffusion for the assessment of unbound haemagglutinin is suggested. 相似文献
19.
Tseng CT Sbrana E Iwata-Yoshikawa N Newman PC Garron T Atmar RL Peters CJ Couch RB 《PloS one》2012,7(4):e35421
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. 相似文献20.
In the event that a vaccine is available during an influenza pandemic, vaccine safety monitoring will occur as part of comprehensive public health surveillance of the vaccination campaign. Though inactivated influenza vaccines have been widely used in the United States and much is known about their safety profile, attention will need to be paid to both common self-limited adverse reactions and rarer, more serious events that may or may not be causally related to vaccination. The primary surveillance systems used to generate and test hypotheses about vaccine safety concerns are the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), respectively. Examples of recent use of these systems to investigate influenza vaccine safety and enhancements planned for use during a pandemic are presented. Ethical issues that will need to be addressed as part of an overall vaccine safety response include risk communication and injury compensation. Advance planning and the use of available technologic solutions are needed to respond to the scientific and logistic challenges involved in safely implementing mass vaccination during a pandemic. 相似文献