Two cases of measles after vaccination with measles mumps and rubella combined live attenuated vaccine / 上海预防医学

Measles is an acute respiratory infectious disease caused by the measles virus. It is highly infectious and easy to occur in children. It causes many serious complications such as tracheitis， otitis media and pneumonia. Since the promotion of the measles vaccine in China， the measles epidemic has been effectively controlled. From June 1， 2020， the immunization procedure of measles-containing vaccine for children in Shanghai has been adjusted to one dose of measles， mumps and rubella combined live attenuated vaccine （MMR） at the age of 8 months， 18 months and 6 years. There is generally no local reaction after the injection of the MMR vaccine. A few individuals may have transient fever and scattered rash， which generally fade away by themselves. However， because it is a live vaccine， it may cause vaccine related diseases in extremely rare cases. This paper reports two cases of measles after vaccination with the MMR vaccine.

Inmunizaciones en niños, adolescentes y adultos inmunosuprimidos / Immunizations in children, adolescent and adult immunocompromised hosts

Los pacientes inmunosuprimidos presentan un riesgo mayor de infecciones, debido a sus disfunciones inmunes, producto de la actividad de su enfermedad y la terapia inmunosupresora. El uso de vacunas disminuye este riesgo, otorgando protección directa e indirecta, a través de la vacunación del paciente y sus contactos. Las vacunas inactivadas han demostrado un perfil de seguridad adecuado en estos pacientes, por lo que no están contraindicadas, aunque su respuesta inmune puede ser inadecuada. Las vacunas vivas atenuadas, formalmente contraindicadas, poseen una información creciente que permite evaluar su riesgo/beneficio de manera individual. Por este motivo es necesario procurar mantener el calendario de vacunas actualizado y complementado, evitando el retraso en esquemas de vacunación y poniéndolo al día lo antes posible, con estrategias basadas en el individuo. Para llevar a cabo esto, se debe conocer y considerar los intervalos entre las vacunas, los esquemas acelerados, la solicitud de vacunas especiales, las aprobaciones vigentes y, finalmente, sus contraindicaciones.

Immunecompromised patients are at higher risk of infections due to their immune dysfunction caused by ongoing disease processes and immunosuppressive therapy. Patient vaccination or vaccination of the people in contact with patients diminishes their risk of infection. Although the immune response of immunocompromised patients might be impaired, the use of inactivated vaccines is safe and it is not contraindicated in these patients. Formerly, live attenuated vaccines were contraindicated in immunecompromised patients, but recently more data supports their use when evaluating case by case the risks and benefits of their application. Thus, it is important to keep and up-to-date, taylor-based and enhanced vaccination schedule in these cases. For this, specialists need to be informed about the availability of regular and special vaccines, their current approvals, vaccine administration protocols under specific situations and vaccine contraindications.

Comparing the antibody titers of sequential program of Sabin strain-based inactivated poliovirus vaccine followed by bivalent types 1 and 3 oral poliovirus vaccine in different dosage forms / 中华疾病控制杂志

Objective To evaluate the antibody titer distributions after primary vaccination by different sequential schedules of Sabin strain-based inactivated poliovirus vaccine(sIPV) and bivalent oral attenuated live poliomyelitis vaccine against types 1 and 3 (bOPV) in Drug Candy(DC) form or liquid dosage form. Methods Eligible infants of 2 months old selected in Liuzhou were assigned randomly in a ratio of 1:1:1:1 to 4 groups as following: sIPV+2bOPV(DC), sIPV+2bOPV(liquid), 2sIPV+bOPV(DC), 2sIPV+bOPV(liquid), and were vaccinated at 0, 28, 56 days. Polio neutralizing antibody titers against poliovirus types 1, 2 and 3 were tested prior to Dose 1 and at 28 days after Dose 3. Results The antibody titer distribution for type 1 was statistically different between sIPV+2bOPV(DC) and sIPV+2bOPV(liquid) (Z=-2.589, P=0.010) while no significant differences were detected between the two groups for type 2(Z=-0.331, P=0.741) and type 3(Z=-1.556, P=0.120). There were no significant differences between 2sIPV +bOPV(DC) and 2sIPV+bOPV(liquid) for the distributions(All P>0.05) (type 1: Z=-1.249, P=0.212; type 2: Z=-1.658, P=0.097; type 3: Z=-1.436, P=0.151). In the same dosage forms with different sequential schedules, the antibody titer distributions were significantly different between 2 doses sIPV and 1 dose sIPV groups(All P<0.05)(sIPV+2bOPV(liquid) vs 2sIPV+bOPV(liquid): type 1: Z=-2.766, P=0.006; type 2: Z=-9.137, P<0.001; type 3: Z=-5.529, P<0.001. sIPV+2bOPV(DC) vs 2sIPV+bOPV(DC): type 1: Z=-3.748, P<0.001; type 2: Z=-7.660, P<0.001; type 3: Z=-6.030, P<0.001). Conclusions Different dosage forms have similar immune effects, so appropriate dosage forms should be selected for vaccination according to the effectiveness, characteristics of subjects and the population density. In the case of sufficient supply of sIPV, 2 doses sIPV sequential program should be the first choice to complete the primary immunization.

Generation and protective efficacy of a cold-adapted attenuated genotype 2b porcine epidemic diarrhea virus

The recent emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) underscore the urgent need for the development of novel, safe, and effective vaccines against the prevailing strain. In this study, we generated a cold-adapted live attenuated vaccine candidate (Aram-P29-CA) by short-term passage of a virulent PEDV isolate at successively lower temperatures in Vero cells. Whole genome sequencing identified 12 amino acid changes in the cold-adapted strain with no insertions and deletions throughout the genome. Animal inoculation experiments confirmed the attenuated phenotype of Aram-P29-CA virus in the natural host. Pregnant sows were orally administered P29-CA live vaccines two doses at 2-week intervals prior to parturition, and the newborn piglets were challenged with the parental virus. The oral homologous prime-boost vaccination of P29-CA significantly improved the survival rate of the piglets and notably mitigated the severity of diarrhea and PEDV fecal shedding after the challenge. Furthermore, strong antibody responses to PEDV were detected in the sera and colostrum of immunized sows and in the sera of their offspring. These results demonstrated that the cold-adapted attenuated virus can be used as a live vaccine in maternal vaccination strategies to provide durable lactogenic immunity and confer passive protection to litters against PEDV.

An attenuated Salmonella vaccine secreting Lawsonia intracellularis immunogenic antigens confers dual protection against porcine proliferative enteropathy and salmonellosis in a murine model

Porcine proliferative enteropathy (PPE) caused by Lawsonia intracellularis (LI) is a global cause for substantial economic losses in the swine industry. Here, we constructed live attenuated Salmonella typhimurium (ST) mutant strains expressing and secreting 4 selected immunogenic LI antigens, namely, optA, optB, Lawsonia flagellin (LfliC), and Lawsonia hemolysin (Lhly); the resultant recombinant strains were designated Sal-optA, Sal-optB, Sal-LfliC, or Sal-Lhly, respectively. Using the BALB/c mouse model, we demonstrate that mice vaccinated once orally, either with a mixture of all 4 recombinant strains or with an individual recombinant strain, show significant (p < 0.05) production of LI-specific systemic immunoglobulin (Ig) G and mucosal IgA responses compared to the Salmonella alone group. Upon restimulation of vaccinated splenocytes with the LI-specific antigens, significant (p < 0.05) and comparable production of interferon-γ responses are found in all vaccinated groups, except the Sal-Lhly group, which shows non-significant levels. Challenge studies were performed in C57BL/6 vaccinated mice. On challenge with the LI (10(6.9) 50% tissue culture infectious dose) 14 days post-vaccination, 20% (1/5) of mice in all vaccinated groups, except Sal-Lhly group, show the presence of the LI-specific genomic DNA (gDNA) in stool samples. In contrast, 40% (2/5) and 60% (3/5) of mice vaccinated with the Sal-Lhly strain and the attenuated Salmonella alone, respectively, were found positive for the LI-specific gDNA. Furthermore, 0% mortality was observed in mice vaccinated against the ST challenge compared to the 30% mortality observed in the unvaccinated control group. In conclusion, we demonstrate that the Salmonella-based LI-vaccines induce LI-specific humoral and cell-mediated immunities, and encompass the potential to offer dual protection against PPE and salmonellosis.

The progress and challenge of Japanese encephalitis control and prevention in China / 中华预防医学杂志

Japanese encephalitis (JE) is the important viral encephalitis in China. In the 1940s, JE was confirmed to be epidemic in China. In 1971, the annual incidence rate was 20.92/100 000. Since 2008, JE vaccine was included in the national Expanded Program of Immunization (EPI). In 2013, the incidence of Japanese encephalitis decreased to 0.16/100 000. JE virus is divided into five genotypes, and genotype 1, 3 and 5 JE virus was isolated in China. Genotype 1 JE virus was the mainly genotype currently circulated in China. In recent years, the characteristics of the population of JE have been changed to adult, especially in the northern provinces of China. JE prevention and control faces new challenges.

Evaluation of pathogen P21 protein as a potential modulator of the protective immunity induced by Trypanosoma cruzi attenuated parasites

BACKGROUND TcP21 is a ubiquitous secreted protein of Trypanosoma cruzi and its recombinant form (rP21) promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerisation in the host cell. OBJECTIVE Our goal was to evaluate if the additional supplementation of rP21 during a prime/boost/challenge scheme with T. cruzi TCC attenuated parasites could modify the well-known protective behavior conferred by these parasites. METHODS The humoral immune response was evaluated through the assessment of total anti-T. cruzi antibodies as well as IgG subtypes. IFN-γ, TNF-α and IL-10 were measured in supernatants of splenic cells stimulated with total parasite homogenate or rP21. FINDINGS Our results demonstrated that, when comparing TCC+rP21 vs. TCC vaccinated animals, the levels of IFN-γ were significantly higher in the former group, while the levels of IL-10 and TNF-α were significantly lower. Further, the measurement of parasite load after lethal challenge showed an exacerbated infection and parasite load in heart and skeletal muscle after pre-treatment with rP21, suggesting the important role of this protein during parasite natural invasion process. MAIN CONCLUSION Our results demonstrated that rP21 may have adjuvant capacity able to modify the cytokine immune profile elicited by attenuated parasites.

Virulence variation and live attenuated vaccines of Japanese encephalitis virus in China / 中华实验和临床病毒学杂志

Chinese scientists have isolated hundreds of Japanese encephalitis virus (JEV) strains from nature and studied their virulence in mice since 1949. They found that the JEV isolates in nature had apparently different virulence among them, especially the pheripheral virulence. This difference was caused by the effects of virus living circumstance such as the mosquito vectors, hosts and natural climate etc. Further studies demonstrated that the virulence of JEV could be reduced in laboratory by serial passages of the virus in mouse brain or different cell cultures especially in hamster kidney cells and the pheripheral virulence was reduced more rapidly. The technique of virus plaque purification was able to differentiate the higher and lower virulent viruses and can be used for selection of avirulent virus strain.By using different ways several attenuated virus strains have been selected and used as live vaccine for vaccination in humans, pigs and horses. Especially, they found that in vivo passage of the viruses in non-neural tissues of laboratory animals could further reduce residual virulence and promote their immunogenicity. By using this creative technology, a highly attenuated, immunogenic and genetically stable attenuated strain SA14-14-2 virus was selected. The attenuated live vaccine made by SA14-14-2 strain has been used worldwild since its licensure in 1989. And in 2013, the vaccine made by Chengdu Biological Institute obtained WHO prequalification.

Safety and Immunological Effects of Measles-mumps-rubella Attenuated Live Vaccine in Children / 中国药房

OBJECTIVE:To observe the safety and immunological effects of Measles-mumps-rubella(MMR)attenuated live at-tenuated vaccine in children. METHODS:300 children aged 8-12 months receiving inoculation were selected from Changsha Hospi-tal for Maternal and Child Health Care during Jan. 2015-Apr. 2016 to observe safety and immunological effects. Those children were divided into MMR group,measles vaccine group,mumps vaccine group and rubella vaccine group according to vaccine type, with 75 cases in each group. The occurrence of ADR in 72 h were compared among 4 groups after inoculation;venous blood of chil-dren was collected before vaccination and 5 months after vaccination,and the antibody positive test was carried out by micro coagu-lation inhibition (HI) test;HI antibody titer was recorded after immunization,and positive rate and genometric meantiter(GMT) were calculated. RESULTS:The incidence of ADR in 4 groups were 9.33%,8.00%,8.00% and 10.67%,respectively. No local ADR was found in 4 groups;among systemic ADR,the incidence of fever was higher than that of other clinical manifestations,be-ing 4.00%,4.00%,4.00% and 5.33%;there was no statistical significance in the incidence of ADR among 4 groups(P>0.05). Measles,mumps and rubella antibody positive rates of MMR group were 100%,92.00% and 100%,respectively;antibody posi-tive rates of measles vaccine group,mumps vaccine group and rubella vaccine group were 100%,85.33% and 100%,respective-ly;there was no statistical significance in same antibody positive rate among 4 groups(P>0.05). GMT of measles in MMR group and measles vaccine group were 1∶41 and 1∶27,that of mumps in MMR group and mumps vaccine group were 1∶6.3 and 1∶6.2, there was no statistical significance (P>0.05);GMT of rubella in MMR group and rubella vaccine group were 1∶320 and 1∶849, with statistical significance (P<0.05). CONCLUSIONS:Compared to traditional single vaccine,MMR dose not increase the inci-dence of ADR and not influence positive rate,but GMT of rubella increases significantly,to which should be paid attention.

Construction of hemolysin hlyA gene knocked out of cholera vaccine candidate and inserted green fluorescent protein gene / 实用医学杂志

Objective To knock down hemolysin hlyA gene and insert green fluorescence protein gene of vibrio cholerae vaccine candidate NFYY101. Methods Amplified fragments of hlyA gene upstream (hlyAup) and downstream (hlyAdown),lacz-GFPuv,and hlyAup-laczGFPuv-hlyAdown, and plasmids treated with specific enzymes were utilized to construct recombinant plasmids pUC18-hlyAup-laczGFPuv-hlyAdown and pCVD442-hlyAup-laczGFPuv-hlyAdown. Following the construction of the recombinant suicide plasmids ,a vaccine candidate was constructed by homologous recombination ,while SM10λpir carrying pCVD442- hlyAup-laczGFPuv-hlyAdown was utilized as the donor strain to transfect NFYY101. Results Construction of recombinant suicide plasmids pCVD442- hlyAup-laczGFPuv-hlyAdown was satisfactory that hemolysin hlyA gene was knocked out and green fluorescence protein gene was successfully inserted of vibrio cholerae vaccine candidate NFYY101. Conclusion Construction of the recombinant suicide plasmid pCVD442-hlyAup-laczGFPuv-hlyAdown successfully can be used for knocked out the hlyA gene and added green fluorescence protein gene as genetic marker into the chromosomal DNA of vibrio cholerae vaccine candidate.

The role of rpoS, hmp, and ssrAB in Salmonella enterica Gallinarum and evaluation of a triple-deletion mutant as a live vaccine candidate in Lohmann layer chickens

Salmonella enterica Gallinarum (SG) causes fowl typhoid (FT), a septicemic disease in avian species. We constructed deletion mutants lacking the stress sigma factor RpoS, the nitric oxide (NO)-detoxifying flavohemoglobin Hmp, and the SsrA/SsrB regulator to confirm the functions of these factors in SG. All gene products were fully functional in wild-type (WT) SG whereas mutants harboring single mutations or a combination of rpoS, hmp, and ssrAB mutations showed hypersusceptibility to H2O2, loss of NO metabolism, and absence of Salmonella pathogenicity island (SPI)-2 expression, respectively. A triple-deletion mutant, SGDelta3 (SGDeltarpoSDeltahmpDeltassrAB), was evaluated for attenuated virulence and protection efficacy in two-week-old Lohmann layer chickens. The SGDelta3 mutant did not cause any mortality after inoculation with either 1 x 10(6) or 1 x 10(8) colony-forming units (CFUs) of bacteria. Significantly lower numbers of salmonellae were recovered from the liver and spleen of chickens inoculated with the SGDelta3 mutant compared to chickens inoculated with WT SG. Vaccination with the SGDelta3 mutant conferred complete protection against challenge with virulent SG on the chickens comparable to the group vaccinated with a conventional vaccine strain, SG9R. Overall, these results indicate that SGDelta3 could be a promising candidate for a live Salmonella vaccine against FT.

A DNA Vaccine versus Attenuated Vaccine to Protect against Salmonella Infection in Chickens.

The aim of this study was to vaccinate layer hen chickens against Salmonella infection. Two vaccines were assessed for efficacy and safety: a DNA vaccine containing Salmonella genomic DNA encapsulated in a liposome as a vector and a live attenuated Salmonella vaccine comprising 5 attenuated Salmonella serovars that were attenuated using indigenous plant extracts such as garlic and onion. The results showed that both vaccines had a high protection capacity, preventing Salmonella infection after challenge with a wild type of SalmonellaTyphimurium. Hyper-immune eggs inhibited the growth of Salmonella spp in vitro in immunized chickens. ELISA demonstrated the specific antibody production to LPS of S. Typhimurium. Post-mortem studies confirmed the presence of salmonellosis in the control group but not in immunized chickens with either vaccine. This study shows that Poultry salmonellosis can be prevented by the use of prophylactic DNA or live-attenuated vaccines (LAV).

Status and progress of research on mucosal vaccines / 中国药学杂志

OBJECTIVE: Mucosal surfaces are a major portal of entry for many human pathogens that are the cause of infectious diseases. Vaccines that immunize by mucosal routes may induce protective immunity against mucosal pathogens at their sites of entry thus to be more effective and economical. We try to overview the status and progress of research on mucosal vaccines. METHODS: The databases of CNKI and Pubmed were used to search the related articles about mucosal vaccines with key words "mucosal vaccine, mucosal adjuvant, mucosal particulate delivery vectors" in Chinese and English. Articles closely related to mucosal vaccines were selected. RESULTS: Thirty-six articles were included at last. Live-attenuated or inactivated mucosal vaccines and vaccines based on new concepts such as subunit vaccines, virus-like particles and virosomes have been marketed, and related research work are undergoing. Safe and effective mucosal adjuvants and delivery vectors are being sought to enhance the magnitude and quality of the protective immune response. The composition, size, surface chemistry and ligands of particulate carrier systems may influence the efficacy. Great progress has been made in several particulate delivery systems. CONCLUSION: Although the research and development of mucosal vaccines are facing many difficulties and challenges, the progress of research work will bring new opportunities to mucosal vaccines development.

Advances in live attenuated vaccines by targeting host microRNAs / 军事医学

Vaccine immunization represents the most effective strategy against viral infections .Antiviral vaccine candi-dates currently include live attenuated vaccine , inactivated vaccine , DNA vaccine and genetic engineering vaccine .Live at-tenuated vaccines , eliciting efficient humoral and cellular immune response by simulating natural virus infection , are clini-cally widely used.Traditionally, live attenuated vaccine strains are obtained by serial passaging in vitro or in vivo, a costly procedure accumulating random mutations .microRNA( miRNA)-targeting host gene regulation exhibits high species and tis-sue specificity .Introducing certain miRNA target sequence into viral genome by reverse genetic technique can effectively attenuate virus strains, which has great potential in vaccine design and development .In this article,attenuation strategies and progress in its application in vaccine research are disscussed .

Construction of a recombinant Neisseria gonorrhoeae strain with rmp gene deletion and study on the bactericidal activities of its antibodies / 中华微生物学和免疫学杂志

Objective To study the role of the outer membrane protein Rmp of Neisseria gonor-rhoeae strain in immunosuppression and the strategy of eliminating it .Methods The rmp gene of Neisseria gonorrhoeae strain was amplified by PCR and inserted into pMD 19-T vector .The recombinant vector pMD 19△rmp∷Kan containing Kan and the 5′-and 3′-flanking regions of rmp (△rmp∷Kan) was constructed by replacing 200 nucleotide residues of pMD 19-rmp with kanamycin resistance gene Kan and transformed into Neisseria gonorrhoeae WHO-A strain.PCR and Western blot assay were used to screen and identify the re-combinant mutant strains that could not express Rmp .Mice were immunized with mutant strains and bacteri-cidal activities of the immune sera were detected by antibody-mediated complement-dependent cytotoxicity assay.Results The mutant strains that could not encode Rmp were successfully constructed .Antibodies in-duced by mutant strains showed stronger bactericidal activity against Neisseria gonorrhoeae in comparison with those induced by wild strains .Conclusion The recombinant Neisseria gonorrhoeae strain with rmp gene de-letion might eliminate the immunosuppressive effects of Rmp expressed in wild gonococcal strains , which provides a reference for further development of novel live attenuated whole-cell vaccines of Neisseria gonor-rhoeae.

Cross-Protective Immune Responses Elicited by Live Attenuated Influenza Vaccines

The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.

Principles underlying rational design of live attenuated influenza vaccines

Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs.

Immunogenicity of Single Dose Live Attenuated Hepatitis A Vaccine.

A long-term immunogenicity study of a single dose live attenuated H2 strain hepatitis A vaccine is being conducted in healthy Indian children at KEM Hospital, Pune. 131 of the original 143 children vaccinated in 2004, were evaluated for anti- HAV antibodies 30 months post vaccination (2007). Seroprotective antibody levels ≥20 mIU/mL were demonstrated in 87.8% subjects with an overall GMT of 92.02mIU/mL. No hepatitis like illness was recorded in any of the subjects since vaccination

The Plasma Load of Inoculated EIAV Vaccine Strain EIAV_(FDDV) Was Not Boosted by Immune Suppression / 生物化学与生物物理进展

The attenuated Chinese equine infectious anemia virus (EIAV) vaccine is the first lentiviral vaccine that provides solid protective immunities to vaccinated horses. To investigate properties of EIAV vaccine, especially the relationship between its replication and the immunity, viral plasma loads of an EIAV vaccine strain EIAVFDDV in immune suppressed horses were detected. Three horses, which were immunized with EIAVFDDV for 16 months, were treated with dexamethasone for 14 days to suppress their immunities. Reduced immune response in these animals was confirmed by significantly declined lymphocyte proliferation rate detected after 10 days of the drug treatment. The plasma viral loads of EIAVFDDV, which was indicated by the genomic RNA copy numbers, in horses before and after the treatment of dexamethasone were monitored by real time RT-PCR. Results revealed that the viral plasma loads in two of three immune-suppressed horses were kept a steady low level around 103～ 104 copies/ml. The load was increased by 10 folds in the third horse, but was still among the standard levels for EIAVFDDV vaccinated horses. As a positive control, the viral copy number of an asymptomatic carrier of EIAV virulent strain EIAVLiao was jumped nearly 25 000-fold higher after being treated with dexamethasone. The typical clinical symptoms of EIA, characterized by febrile episodes and thrombocytopenia, were also appeared in this horse. These results clearly indicate that it is the unique biological feature of the attenuated EIAV vaccine, but not the immunity, resulted in EIAVFDDV remaining in low levels in the body harmlessly. In addition, the steady low level of viremia and the inability to cause clinical symptoms of EIAVFDDV in immune-suppressed hosts further demonstrated the safety of attenuated Chinese EIAV vaccines. The data provide a new sight for studies on the immunity to lentiviruses.

HUMAN PAPILLOMAVIRUS TYPE 16 L1 PROTEIN CAN BE EXPRESSED IN LIVE ATTENUATED SHIGELLA FLEXNERI 5A STRAIN SH42 / 药物分析学报

Objective Attenuated strains of Shigella are attractive live vaccine candidates for eliciting mucosal immune responses which is a suitable carrier for the prophylactic human papillomaviruses (HPV) vaccine development, To examine the potential of a live Shigella based prophylactic HPV vaccine, HPV16L1should be expressed in attenuated shigella strain. Methods A Shigella large invasive plasmid (icsA/virG) based prokaryotic expression plasmid pHS3199 was constructed. HPV16L1 gene was inserted into plasmid pHS3199 to form pHS3199-HPV16 L1 construct, and pHS3199-hpv16L1 was electroporated into a live attenuated shigella strain sh42. The expression of HPV16L1 protein was demonstrated by Western blotting with monoclonal antibody to HPV16L1, The genetic stability of recombinant strain sh42-HPV16 L1 was monitored by consecutive passage culture. Invasive ability of sh42-HPV16L1 was evaluated by Hela cell infection assay. Results HPV16 L1 protein can be expressed in recombinant strain sh42-HPV16 L1, and the protein stably expressed over 140 generations. The invasive ability of sh42-HPV16L1 was diminished dramatically compared to its parent strain, but not abolished completely. Conclusion HPV16L1 protein was constitutively expressed in the attenuated strain of shigella flexneri sh42, and maintained partial invasive ability. Our strategy may represent a promising vaccine candidate against genital HPV16 infection.