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@#Vaccines with novel adjuvants have been listed abroad,while in China,except for aluminum adjuvants widely used in vaccine research and production,few other novel adjuvants have been successfully listed. This paper briefly summarized the source,development history,research progress on biological activity and immune mechanism as well as safety evaluation of the novel BC adjuvant system with independent intellectual property right which has been applied to the vaccine in clinical research stage,so as to provide theoretical support for selection of the adjuvant in the development of novel vaccine.
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Since the end of 2019, the COVID-19 caused by 2019-nCoV has emerged and the pandemic ravaged the world, which seriously threatens global public health security and economic development. 2019-nCoV vaccine is an effective weapon to combat the viral infection, however, studies have shown that vaccine-induced immune protection decreases over time, coupled with some novel and immune escape variants continual emerging. Therefore, it is urgent to complete booster immunization to improve protection. At present, 2019-nCoV vaccines based on a variety of technical platforms have been approved and available in China. Therefore, we developed this sequential vaccination strategy guide to provide documentation guidance for the prevention and control of the epidemic caused by 2019-nCoV and its variant strains.
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The definition of adjuvant in immunology is the non-specific immunopotentiator, which only performs auxiliary functions. With the appearance of various adjuvants and their successful application in some vaccines against infectious disease, they have received extensive attention and been studied in-depth. This review focused on the types, functions and prospects of adjuvants used in tuberculosis vaccines, aiming to provide reference for adjuvant selection and development in future.
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OBJECTIVE To investigate nonclinical safety and immunogenicity of the recombinant nine-valent human papillomavirus vaccine(9vHPV vaccine) through repeated dose to rats, and provide reference for the dose level design and side effects monitoring in clinical trials. METHODS: Wistar rats were used and divided into four main toxicity groups: negative control, adjuvant control, low dose HPV vaccine group(1/2 dose•rat-1) and high dose HPV vaccine group(2 dose•rat-1). Each group had a satellite group. Animals were dosed by intramuscular injection in weeks 0, 2, 4 and 6 respectively. During the study, all the animals were observed for clinical signs and injection site irritations. For main toxicity groups, body weights, food consumption and body temperature were measured, and ophthalmologic examination, urinalysis, hematology, coagulation, serum chemistry examinations and T lymphocyte subset assay in peripheral blood were done at terminal and recovery necropsy respectively. A full necropsy was then conducted on animals, and tissues were weighed and processed for microscopic examination. Serum anti-HPV binding antibody and neutralizing antibody and antinuclear antibody were determined for satellite animals. RESULTS: Rats produced high levels of anti-HPV binding antibody and neutralizing antibody with strong activity to the nine antigens contained in the low and high dose HPV vaccines. The low and high dose vaccine and the adjuvant caused the increases in peripheral blood neutrophils and eosinophils, which basically recovered three weeks post the last dose. Both the adjuvant and the two dose levels of vaccine led to the slight decrease in serum ALB, increase in globulin and the decrease in A/G ratio in treated rats. Adjuvant and vaccine-related gross necropsy changes were white spots in bilateral injection site muscles. Treatment-related microscopic findings were the degeneration and necrosis of muscle fibers, mixed inflammatory cell infiltration and hyperplasia of fibrous tissue in injection site muscles, and the mixed inflammatory cell infiltration and hyperplasia of fibrous tissue around the sciatic nerve sheath, which partially recovered at the end of the recovery period. The HPV vaccine did not have obvious impact on other end points determined. CONCLUSION: The low and high dose vaccine and the adjuvant can cause the following changes in rats: the increases in peripheral blood neutrophils and eosinophils, the increase in serum globulin and the pathological irritation changes at injection sites. The 9vHPV vaccine has a good safety profile in Wistar rats under the dose levels of this study, with the no observed adverse effect level of 2 dose•rat-1.
ABSTRACT
OBJECTIVE: To investigate nonclinical safety of the novel CpG 684-rabies vaccine through repeated dose to BALB/c mice, and provide reference for the dose level design and side effects monitoring in clinical trials. METHODS: BALB/c mice were used and divided into five treatment groupsvehicle control, rabies vaccine control, (2.5 μg CpG 684+1/4 rabies vaccine)·mouse-1, (5 μg CpG 684+1/4 rabies vaccine)·mouse-1 and (15 μg CpG 684+1/4 rabies vaccine)·mouse-1 treated groups. Animals were dosed by intramuscular injection on days 0, 3, 7, 14, 28 and 42. During the study, each animal was observed for clinical signs and injection site irritations. Body weights and food consumption were measured. Serum anti-rabies IgG antibody and IgG2a antibody were determined. Hematology and serum chemistry examinations were conducted respectively 1 day and 3 weeks post the last dose. A full necropsy was then conducted on animals, and tissues were weighed and processed for microscopic examination. RESULTS: Rabies vaccine alone and all dose levels of CpG 684-rabies vaccine caused severe allergic reactions after the fourth, fifth or sixth dose in mice. After the last administration, each dose of CpG 684-rabies vaccine caused the increase in monocyte in both sexes of mice and the decrease in platelet in female mice, and high dose of CpG 684-rabies vaccine also induced the decrease in platelet in male mice. High dose of CpG 684-rabies vaccine led to the increase in serum CHO in both sexes of mice. Rabies vaccine alone and middle and high doses of CpG 684-rabies vaccine induced the decrease in serum ALP in mice. All the above changes recovered three weeks post the last dose. Rabies vaccine alone and all dose levels of CpG 684-rabies vaccine caused the increase in serum globulin and the decrease in A/G ratio in male and female mice, which did not recover 3 weeks post the last dose. Rabies vaccine alone and all dose levels of CpG 684-rabies vaccine induced the increase in spleen weight, which recovered to some degree 3 weeks post the last dose. Treatment-related microscopic findings were cell hyperplasia in white pulp of spleen and the increase in tingible body macrophages in germinal center of white pulp, and the marked inflammatory reaction and hyperplasia of fibrous tissue in injection site muscle, which basically vanished at the end of the recovery period except the high dose group. CONCLUSION: Rabies vaccine alone and CpG 684-rabies vaccine cause severe allergic reactions, the increases in serum globulin and spleen weight and the decrease in serum ALP. CpG 684-rabies vaccine induces the decrease in platelet and the increases in monocyte and serum CHO. Treatment-related microscopic findings are cell hyperplasia in white pulp of spleen and the increase in tingible body macrophages in germinal center of white pulp, and the marked inflammatory reaction and hyperplasia of fibrous tissue in injection site muscle. Most of the changes recover 3 weeks post the last dose.