Revisiting the Chingleput BCG vaccination trial for the impact of BCG revaccination on the incidence of tuberculosis disease

Background & objectives: Vaccines play a crucial role in the prevention of tuberculosis (TB). Revaccination with Bacille Calmette–Guerin (BCG) for the prevention of TB is an important strategy that is currently gaining interest. The objective of this study was to reanalyze the community-based Chingleput BCG vaccination trial for protective efficacy of BCG revaccination against incident TB disease. Methods: A retrospective analysis of the Chingleput BCG vaccination trial (conducted in 1968) data was carried out. Data on participants with evidence of prior BCG vaccination at trial intake and randomized to BCG vaccine [low dose (0.01 mg), high dose (0.1 mg)] and placebo arms were analyzed. The incidence of TB disease, which was based on sputum culture and/or chest X-ray was compared between the BCG and placebo arms over a 15 yr follow up period. Results: Of the 269,727 individuals randomized in the trial; 263,158 had no evidence of TB at baseline, of which 4436 (1.68%) had evidence of BCG vaccination at trial intake (2890 in the BCG vaccine and 1546 in the placebo arms, respectively). There were 77 (190 per 100,000) and 64 (296 per 100,000) incident TB cases in the BCG and placebo arm, respectively, at 15 yr post-vaccination. The incidence of TB disease was significantly lower in the BCG arm [Hazard ratio of BCG arm (95% confidence interval): 0.64 (0.46-0.89)]. Interpretation & conclusions: Retrospective data analysis of this community-based trial revealed that BCG revaccination in a community offered modest protection against the development of TB disease at the end of 15 years which, however, requires further evaluation.

Research progress in the protective efficacy of human papillomavirus vaccines in males / 中华微生物学和免疫学杂志

Human papillomavirus (HPV) is one of the most common sexually transmitted pathogens. It can cause a variety of diseases such as condyloma acuminatum, anal cancer, penile cancer and oropharyngeal cancer in men, resulting in a high disease burden. With the development of society, the application of HPV vaccines in males has attracted more attention. Currently, there are many clinical trials and real-world research results of HPV vaccines applied to boys and men worldwide, and many countries have introduced HPV vaccination for underage boys into their national immunization programs. This article intended to review the research progress in the efficacy of HPV vaccines in male population.

Blocking effect of SARS-CoV-2 vaccines on virus transmission: current situation and prospect / 中华微生物学和免疫学杂志

SARS-CoV-2 vaccines are effective in preventing COVID-19, but their efficacy in blocking virus transmission is controversial. Although SARS-CoV-2 vaccines can reduce the sources of infection and the possibility of secondary transmission from breakthrough infection cases, their effectiveness wanes over time. Moreover, the emergence of variants with stronger transmissibility and immune escape ability also poses huge challenges to the effectiveness of SARS-CoV-2 vaccines in blocking virus transmission. Therefore, ending the COVID-19 pandemic still requires the continuous research and development of new vaccines as well as the adoption of effective prevention and control measures.

Tandem expression of the major epitope domains of the Moschus chrysogaster hemorrhagic disease virus VP60 and its protective efficacy to rabbits / 生物工程学报

Moschus chrysogaster (sifanicus) viral hemorrhagic disease (McVHD) is an acute and highly lethal infectious disease caused by Moschus chrysogaster hemorrhagic disease virus (McHDV) whose genome sequence is highly homologous with rabbit hemorrhagic disease virus. To screen the protective antigen of McHDV and set the basis for study of McVHD vaccine, the antigen epitope of major structural protein VP60 of McHDV was analyzed, and the specific primers were designed to obtain three amplified DNA sequences encoding the main antigen epitope of VP60 from McHDV by using RT-PCR. Then the three DNA fragments were sequenced and cloned to prokaryotic expression vector with pET-28a(+) by using overlap extension PCR, and finally the prokaryotic expression plasmid pET-truncated-VP60 was constructed. Subsequently, the pET-truncated-VP60 was transformed into Escherichia coli BL21(DE3), and the recombinant proteins were expressed by IPTG induction. Finally, the expressed protein was purified and applied to immunize that without immunizing with RHD vaccine, then the antiserum titers were evaluated by the hemagglutination inhibition test, and the immune-protective efficacy of the recombinant proteins was observed and analyzed through animal challenge test. The results showed that the multi-epitope DNA fragments of VP60 of McHDV was successfully expressed in the form of inclusion bodies in E. coli, and the relative molecular weight of recombinant proteins is about 45 kDa. After immunized with the recombinant proteins, 100% of New Zealand white rabbits were resistant to attack of McHDV, which indicates efficient immune-protective efficacy of chosen epitope recombinant protein. The study laid a foundation for the development of the new subunit vaccines of McVHD.

Progress in research of clinical trials of herpes zoster vaccines / 中华疾病控制杂志

Herpes zoster (HZ) is more common in middle-aged and elderly people, and is caused by varicella-zoster virus (VZV) that is latent in sensory ganglia. In recent years, due to various reasons, especially the aging of China's population has become more serious, the incidence of HZ in China has risen sharply. Although HZ is self-limited, its complications will still reduce the quality of life of patients and increase the economic burden of patients' families and society. In order to reduce the incidence and improve the quality of life of the elderly in their later years, the development of safe and effective HZ vaccine may be an important and effective measure. This article aims to make a brief review of the progress in research for clinical trials of HZ vaccines, so as to provide a reference for the use of HZ vaccine and the prevention and control of HZ disease in China.

Vaccination of goats with a combination Salmonella vector expressing four Brucella antigens (BLS, PrpA, Omp19, and SOD) confers protection against Brucella abortus infection

Salmonella is an intracellular pathogen with a cellular infection mechanism similar to that of Brucella, making it a suitable choice for use in an anti-Brucella immune boost system. This study explores the efficacy of a Salmonella Typhimurium delivery-based combination vaccine for four heterologous Brucella antigens (Brucella lumazine synthase, proline racemase subunit A, outer-membrane protein 19, and Cu/Zn superoxide dismutase) targeting brucellosis in goats. We inoculated the attenuated Salmonella delivery-based vaccine combination subcutaneously at two different inoculation levels; 5 × 10⁹ colony-forming unit (CFU)/mL (Group B) and 5 × 10¹⁰ CFU/mL (Group C) and challenged the inoculations with virulent Brucella abortus at 6 weeks post-immunization. Serum immunoglobulin G titers against individual antigens in Salmonella immunized goats (Group C) were significantly higher than those of the non-immunized goats (Group A) at 3 and 6 weeks after vaccination. Upon antigenic stimulation, interferon-γ from peripheral blood mononuclear cells was significantly elevated in Groups B and C compared to that in Group A. The immunized goats had a significantly higher level of protection as demonstrated by the low bacterial loads in most tissues from the goats challenged with B. abortus. Relative real-time polymerase chain reaction results revealed that the expression of Brucella antigens was lower in spleen, kidney, and lung of immunized goats than of non-immunized animals. Also, treatment with our combination vaccine ameliorated histopathological lesions induced by the Brucella infection. Overall, the Salmonella Typhimurium delivery-based combination vaccine was effective in delivering immunogenic Brucella proteins, making it potentially useful in protecting livestock from brucellosis.

Effect of immunization routes and protective efficacy of Brucella antigens delivered via Salmonella vector vaccine

An anti-Brucella vaccine candidate comprised of purified Brucella lipopolysaccharide (LPS) and a cocktail of four Salmonella Typhimurium (ST)-Brucella vectors was reported previously. Each vector constitutively expressed highly conserved Brucella antigens (rB), viz., lumazine synthase (BLS), proline racemase subunit A, outer membrane protein-19 (Omp19), and Cu-Zn superoxide dismutase (SOD). The present study determined a relative level of protection conferred by each single strain. Upon virulent challenge, the challenge strain was recovered most abundantly in non-immunized control mice, with the ST-Omp19-, ST-BLS-, LPS-, and ST-SOD-immunized mice showing much less burden. Indirect enzyme-linked immunosorbent assay-based assay also confirmed the induction of antigen-specific immunoglobulin G for each antigen delivered. In a route-wise comparison of the combined vaccine candidate, intraperitoneal (IP), intramuscular (IM), and subcutaneous immunizations revealed an indication of highly efficient routes of protection. Splenocytes of mice immunized via IM and IP routes showed significant relative expression of IL-17 upon antigenic pulsing. Taken together, each of the Brucella antigens delivered by ST successfully induced an antigen-specific immune response, and it was also evident that an individual antigen strain can confer a considerable degree of protection. More effective protection was observed when the candidate was inoculated via IP and IM routes.

Towards development of a universal dengue vaccine – How close are we?

Dengue has been ranked as one of the top emerging diseases in Asia and Latin America. Current epidemiological data may not even reflect the true burden of disease due to under-reported figures. Vector control programmes have failed to contain the disease and worst of all, no specific treatment is available at the moment. Thereby, this pushes the demand for a dengue vaccine as a long-term protective approach. Despite there are numerous vaccine candidates ahead, they could be held back by different aspects in promoting vaccine implementation. Particularly for developing nations, logistics and cost are the major hurdles that need to be addressed in order to provide a quick yet affordable medical relief. As an alternative, plant-based vaccine production system is able to offer an attractive prospect given to its advantages of biocontainment warranty, low operation cost, rapid scalability and logistics flexibility. Researches that have embarked on this scope are laid out and reviewed in terms of the feasibility of plant system to serve as a biofactory for dengue vaccine.

A meta-analysis of effectiveness of influenza vaccine in the elderly in China / 预防医学

Objective To evaluate the protective efficacy of influenza vaccine in the elderly in China. Methods The Chinese databases (CNKI, Wan Fang, VIP) and English databases (Pubmed, Embase) were searched, then studies related to the protective efficacy of influenza vaccine in the elderly according to pre-designed criteria were included and the vaccine efficacy(VE) was selected as an evaluation index. Rev Man 5.3 and Stata 12.0 were used in this meta analysis. Results A total of 26 studies (2000-2016) including 6 kinds of outcomes were eligible, of which, 22 articles related to influenza like illness (ILI) , 5 articles related to common cold (CC) , 11 articles related to the attendance rate due to ILI and CC, 7 articles about chronic diseases (including Hypertension, Diabetes, Coronary Heart Disease (CHD) , Stroke, Cancer, Chronic bronchitis and others) , 6 articles about chronic disease treatment and 3 articles about all-cause mortality. The VE of influenza vaccine was 58.00% (95%CI: 48.00%-66.00%), 40.00%(95% CI: 30.00%-50.00%), 42.00% (95% CI: 34.00%-49.00%), 17.00% (95% CI: 11.00%-23.00%), 28.00%(95% CI: 14 .00 % -40.00 %) and 28 .00 % (95% CI: 15 .00 % -39 .00 %) , respectively. Conclusion Influenza vaccination can effectively prevent the occurrence of influenza like disease and other symptoms in the elderly in China.

Towards development of a universal dengue vaccine - How close are we?

Dengue has been ranked as one of the top emerging diseases in Asia and Latin America. Current epidemiological data may not even reflect the true burden of disease due to under-reported figures. Vector control programmes have failed to contain the disease and worst of all, no specific treatment is available at the moment. Thereby, this pushes the demand for a dengue vaccine as a long-term protective approach. Despite there are numerous vaccine candidates ahead, they could be held back by different aspects in promoting vaccine implementation. Particularly for developing nations, logistics and cost are the major hurdles that need to be addressed in order to provide a quick yet affordable medical relief. As an alternative, plant-based vaccine production system is able to offer an attractive prospect given to its advantages of biocontainment warranty, low operation cost, rapid scalability and logistics flexibility. Researches that have embarked on this scope are laid out and reviewed in terms of the feasibility of plant system to serve as a biofactory for dengue vaccine.

Effect and mechanism of CD4+CD25+regulatory T cells on protective effica-cy of protein vaccine against Schistosoma japonicum in mice / 中国血吸虫病防治杂志

Objective To explore the effect and mechanism of CD4+CD25+Tregs(Tregs)on the protective efficacy of glutha?tione?S?transferase(GST)against Schistosoma japonicum in mice. Methods Female BALB/c mice were divided randomly into five groups:a normal control group,an infected control group,an anti?CD25mAb group,a GST immunization group and a com?bination group with GST immunization and anti?CD25 mAb. The GST group and combination group were injected percutaneously with GST 50μg each mouse,the other two groups were injected with equal volume PBS. The immunization was performed for 3 times for two?week interval,and 2 weeks after the last immunization,each mouse was challenged with 40 S. japonicum cercaria. Two weeks post?infection,the combination group and anti?CD25 mAb group were injected intraperitoneally with 300μg anti?CD25 mAb each mouse. The mice were succumbed 2 weeks,3 weeks,4 weeks and 5 weeks post?infection respectively. The per?centages of CD4+CD25+Tregs in splenocytes of mice were measured with flow cytometer. The levels of IFN?γ,IL?2,IL?4,IL?5 and TGF?βin cell cultural supernatants were determined by sandwich?ELISA after stimulation with Con A. The liver sections were stained with hematoxylin and eosin. Results The worm burden in the combination group(15.80 ± 2.74)was significantly lower than those of the infected control group(27.78 ± 3.15),anti?CD25 mAb group(21.50 ± 4.21),and GST group(20.84 ± 6.46). Compared to those of the infected control group,the percentages of CD4+CD25+Tregs were significantly higher in the GST group,while the percentages of CD4+CD25+Tregs were significantly lower post?anti?CD25 mAb?administration. Regardless of GST administration,the levels of IFN?γ,IL?2,IL?4 and IL?5 after anti?CD25 mAb were significantly higher than those of the in?fected control groups. There were no significant differences of egg granuloma and the level of TGF?βbetween each group. Con?clusion CD4+CD25+Tregs could be partially blocked by anti?CD25 mAb while Th1 and Th2 type immunization response could be enhanced,which plays a role in improving the protective efficacy of GST against of S. japonicum.

A meta -analysis of vaccine efficacy of haemophilus influenza type b vaccine among children under five years of age / 预防医学

Objective To evaluate vaccine efficacy(VE)of Haemophilus influenza type b vaccine (Hib)among children under five years of age .Methods Searching “National Center for Biotechnology Information,NCBI”,“Cochrane Library, CL”,“China Biology Medicine disc,CBMd”,“China National Knowledge Infrastructure,CNKI”,“Wanfang Database, the studies of VE for Hib among children under five years of age were included,and meta -analysis were made by RevMan 5.3 software.Results A total of 9 studies were included,seven were randomised clinical trial(RCT)design and two were semi RCT design.The VEs of one dose,two doses and three doses of Hib were 65%(95%CI:23% -84%),79%(95%CI:54% -90%),and 85%(95%CI:77% -90%),respectively.Conclusion We found that Hib is highly effective and that the two dose regime is as good as the three dose regime.

Protective efficacy of a high-growth reassortant swine H3N2 inactivated vaccine constructed by reverse genetic manipulation

Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from the 2009 H1N1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the United States, indicating that H3N2 SwIV might be a potential threat to public health. Since southern China is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the possibility of SwIV infection at agricultural fairs. In this study, a high-growth reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and tested as a candidate inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed, with significantly reduced lung lesion and viral loads in vaccine-inoculated mice relative to mock-vaccinated controls. These results suggest that the GD/PR8 vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV outbreaks in China.

Enhancement of the epitope vaccines from new gene wx2b4a of Toxoplasma gondii potency using pidotimod in mice / 中华微生物学和免疫学杂志

Objective To observe the effect of pidotimod to enhance the immune response and protective immunity induced by the epitope vaccines from new gene wx2b4a of Toxoplasma gondii in mice.Methods Mice were divided into four groups,each group was inoculated intramuscularly three times with pcDNA3-W2b4a,pcDNA3-W2b4a and pidotimod,pcDNA3,natural saline (NS),respectively.The induced immune responses were tested by ELISA detecting IgG,and flow cytometry sorting the subsets of T lymphocyte.All mice were challenged with highly virulent RH tachyzoites to observe the survival time.Results After the immunization,the level of IgG in sera of mice inoculated with wx2b4a and pidotimod,wx2b4a were significantly higher than those control group(all P＜0.05).CD4+ and CD8+T cell counts in immunized groups were higher than those control group(P＜0.05).After the immunization,CD4+T cell counts and CD4+/CD8+T cell proportion in wx2b4a and pidotimod groups were higher than those in wx2b4a group (all P＜0.05).After challenged with highly virulent tachyzoites,the mean survival time of wx2b4a and pidotimod groups was significantly longer than control group and wx2b4a group (all P＜0.05).Conclusion Pidotimod can increase protective immunity of epitope vaccines from new gene wx2b4a of Toxoplasma gondii in mice.

Eficacia protectora de la vacuna Heberbiovac HB® a diferentes dosis en niños impedidos físicos y mentales / Protective efficacy of Heberbiovac HB® at different dosage in physically and mentally-handicapped children

INTRODUCCION: los estudios de seguimiento de eficacia protectora en grupos de alto riesgo a la infección por el virus de la hepatitis B, inoculados con vacunas recombinantes contra la hepatitis B, son limitados, y la duración de la protección aún no está del todo definida en los vacunados contra esta enfermedad. OBJETIVOS: determinar la eficacia protectora de la vacuna Heberbiovac HB® a diferentes dosis en niños impedidos físicos y mentales, 14 años después de aplicado el esquema primario de vacunación. MÉTODOS: en 1991 se realizó un estudio de efectividad con la vacuna Heberbiovac HB® en 2 grupos de niños impedidos físicos y mentales (A= 10 µg y B= 5 µg). El estudio fue aprobado por los Comités de Ética Médica y Revisión del Instituto de Medicina Tropical "Pedro Kourí" y el Centro de Ingeniería Genética y Biotecnología de Ciudad de La Habana; se siguieron las Buenas Prácticas Clínicas vigentes en Cuba y los principios éticos de la Declaración de Helsinki. Se empleó el esquema de vacunación 0, 1 y 6 meses, fueron incluidos los niños que resultaron negativos al antígeno de superficie del virus de la hepatitis B y al anticuerpo contra el antígeno de superficie del virus de la hepatitis B. Los sujetos se estudiaron desde el punto de vista clínico y serológicamente, hasta 14 años después de aplicado el esquema de vacunación. RESULTADOS: 1 año después del comienzo de la vacunación la seroprotección fue de 100 por ciento en ambos grupos. A los 14 años de seguimiento, ningún sujeto resultó positivo al antígeno de superficie del virus de la hepatitis B ni padeció hepatitis B aguda, lo cual resultó en 100 por ciento de protección individual. CONCLUSIONES: el poder inmunogénico de la vacuna Heberbiovac HB® fue elevado y su eficacia protectora fue de 100 por ciento en los niños impedidos físicos y mentales, en el seguimiento clínico serológico realizado hasta 14 años después de la aplicación del esquema de vacunación, resultados obtenidos por primera vez en Cuba para esta vacuna.

INTRODUCTION: the protective efficacy follow-up studies in high risk groups for hepatitis B virus infection, which were inoculated with recombinant hepatitis B vaccines, are limited and the duration of protection is yet to be determined in those vaccinated people. OBJECTIVES: to determine the protective efficacy of Heberbiovac HB® vaccine at different dosage in physically and mentally-handicapped children after 14 years of the primary vaccination schedule. METHODS: in 1991, an effectiveness study of vaccine Heberbiovac HB® was conducted in 2 groups of physically and mentally-handicapped (A=10 µg y B= 5 µg). The study was approved by the Committees of Medical Ethics and Revision of "Pedro Kourí" Tropical Medicine Institute and of the Center of Genetic Engineering and Biotechnology of the City of Havana; good clinical practice were followed and the ethical principles of Helsinki Declaration were respected for. The vaccination schedule at 0, 1 and 6 months was used in which children negative to hepatitis B virus surface antigen and to hepatitis B virus surface antigen antibody were included. The subjects were studied from the clinical and serological viewpoints up to 14 years after the implementation of the aforementioned vaccine schedule. RESULTS: one year after the beginning of the vaccination, there was full seroprotection in both groups. After 14 years of follow-up, none of the subjects was positive to hepatitis B virus surface antigen, neither were they affected by acute hepatitis B, which meant 100 percent individual protection. CONCLUSIONS: the immunogenic power of Heberbiovac HB® vaccine was high and its protective efficacy was 100 percent in physically and mentally-handicapped children according to the results of the clinical and serological follow-up extending up to 14 years after the implementation of the primary vaccination schedule. These results are achieved for the first time for this kind of vaccine.

BCG vaccinaton scars of childen under five years in a tertiary care hospital.

Objective To study the BCG vaccination scars of under 5 year old children who were admitted to a tertiary care hospital Design Cross sectional descriptive study Setting Ward 3, Lady Ridgeway Hospital for Children (LRH) Method All children between 6 and 60 months of age, admitted to ward 3 LRH from October 15th to December 30th 2006, were included in the study. The interviewer-administered questionnaire and examination of the child for BCG scar were the methods used to collect the data. Results: Of 1010 patients admitted to ward 3 LRH during the study period, 923 were analysed. BCG vaccine had been given to all patients. Whilst 821 (89%) patients had the BCG scar, 102 (11%) did not have it. Among patients with the BCG scar, 20% had received BCG vaccine in non tertiary care hospitals, whereas in patients with absent BCG scar, this figure was 35% (p=0.003; p < 0.05). In the Child Health Development Record (CHDR), the BCG scar column had been marked in only 554 (64%). Among 102 patients with absent BCG scar, revaccination was not indicated in 20 (21%) because the BCG scar had been marked as positive in the CHDR. However, 96 had not been revaccinated. Common reasons for non revaccination were: unawareness of mothers regarding absent BCG scar (38.5%) and postponement of revaccination (24%). Conclusion There was a significant number of patients with absent BCG scars indicating need for larger scale studies.

The Meta Analysis of Protective Efficacy of Attenuated Live Hepatitis A Vaccine / 中国疫苗和免疫

Objective To evaluate protective efficacy of attenuated live hepatitis A vaccine.Methods We searched MEDLINE,EMBASE,CNKI.The randomization,concealment of allocation and blinding were included in the study. Results Meta analysis based on included studies showed that both strain of H2 and L-A-1 attenuated live hepatitis A vaccine had good protective efficacy,the protective efficacy is related to the titer of vaccine.The titer

DNA Prime-BCG Boost Vaccination Strategy Improved The Protective Efficacy Against M. tuberculosis H37Rv in Mice / 生物化学与生物物理进展

The immunogenicity and protective efficacy of combined DNA priming, Bacillus Calmeette Guerin(BCG) boosting vaccination in mice were examined. Following intravenous challenge with virulent M. tuberculosis H37Rv, the BCG boost approach resulted in significant protection in both lungs (1.3, P

Immuno-protection efficacy of Mtb8.4 gene vaccine with signal peptide against TB in mice / 基础医学与临床

Objecticve To study the immunogenicity and protective effecacy of MTB8.4 with signal peptide gene vaccine against TB in mice.Methods C57BL/6N!mice were vaccinated with MTB8.4 with signal peptide(MS) gene vaccine three times at 3 weeks intervals.Four weeks after the final vaccination,three mice were sacrificed to assess cytokine response and CTL induction and the other five mice were challenged intravenously in a lateral tail vein with(1?10~(6)) CFU of virulent M.tuberculosis H37Rv.Spleen and the left lung were harvested from each mouse 4 weeks after(infection) and homogenized in sterile saline.Serial dilutions of organ homogenates were plated on (L-J agar) and incubated(37 ℃) until colonies were visible 4 weeks later. Protective efficacy in each experiment was expressed as(reduced) CFU and was compared with the negative control group.The right lung was obtained from each mouse and(inflated) with and stored in 10% formalin saline immediately.Tissues were embedded in paraffin,sec-tioned(and stained) with hematoxylin and eosin.Results MS gene vaccine induced the secretion of more of Th1 cytokines(IFN-?and IL-2),but not IL-4 and enhanced CTL activity while BCG induced the secretion of both types of cytokines(IFN-?,IL-2 and IL-4).Mice immunized with MS gene vaccine had fewer and smaller tubercles than those immunized with PBS or control plasmid DNA,but had more tubercles than the mice inoculated with BCG.Virable bacterial counts in the lungs and spleens of mice receiving DNA encoding MS were reduced as compared with mice injected with PBS or control plasmid DNA,while increased as compared with mice immunized with BCG.Conclusion MS gene vaccine can induce secretion of Th1 cytokines and the higher protective efficacy against TB in mice.

Protective Efficacy of Recombinant Proteins Adenylate Kinase, Nucleoside Diphosphate Kinase, and Heat-Shock Protein 70 against Mycobacterium tuberculosis Infection in Mice / 결핵및호흡기질환

BACKGROUND: Priming and boosting vaccination strategy has been widely explored for new vaccine development against tuberculosis. As an effort to identify other vaccine candidates, this study was initiated to evaluate protective efficacy of adenylate kinase (AK), nucleoside diphosphate kinase (NdK), and heat shock protein 70 (Hsp70) of Mycobacterium tuberculosis. METHOD: M. tuberculosis genes encoding AK, NdK, and Hsp70 proteins were amplified by PCR and cloned into E. coli expression vector, pQE30. Recombinant AK, NdK, and Hsp70 was purified through Ni-NTA resin. To evaluate immune responses, we performed enzyme-linked immunosorbent assay (ELISA) for IgG isotype and IFN-gamma after mice were immunized subcutaneously with recombinant proteins delivered in dimethyl dioctadecylammonium bromide (DDA). Immunized- and control groups were challenged by aerosol with M. tuberculosis. The spleens and lungs of mice were removed aseptically and cultured for CFU of M. tuberculosis. RESULT: Vaccination with recombinant proteins AK, NdK, and Hsp70 delivered in DDA elicited significant level of antibody and IFN-gamma responses to corresponding antigens but no protective immunity comparable to that achieved with Mycobacterium bovis BCG. CONCLUSION: Recombinant proteins AK, NdK, and Hsp70 do not effectively control growth of M. tuberculosis in mice when immunized with DDA as an adjuvant.