Mingbo Sun

Safety and Immunogenicity of Inactivated Poliovirus Vaccine Made From Sabin Strains: A Phase II, Randomized, Positive-Controlled Trial

BACKGROUND The production of Sabin inactivated poliovirus vaccine (IPV) can reduce biosafety requirements in the posteradication/post-oral poliovirus vaccine (OPV) era. We conducted a phase II, randomized, positive-controlled trial to assess the safety and immunogenicity of Sabin IPV. METHODS The test groups (A, B, and C) received 3 doses of high, middle, and low D antigen (D Ag) of Sabin IPV at ages 2, 3, and 4 months, respectively. Infants in 2 control groups, group D and group E, received 3 doses of trivalent OPV and conventional IPV (cIPV), respectively, on the same schedule as that of groups A, B, and C. Serum samples were collected before and 30 days after the administration of the third dose. RESULTS In total, 500 infants were randomly assigned to 5 groups, and 449 infants completed the vaccine series. No serious adverse events were associated with vaccinations. After 3 doses, the seroconversion rates in groups A, B, C, D, and E were 100%, 97.8%, 96.6%, 100%, and 90.1%, respectively, for type 1 poliovirus; 97.7%, 95.7%, 78.7%, 100%, and 90.1%, respectively, for type 2; and 98.8%, 98.9%, 93.3%, 100%, and 97.8%, respectively, for type 3. CONCLUSIONS Sabin IPV has good safety characteristics. The seroconversion rates for type 1 poliovirus (most appropriate concentration, 15 D Ag units [DU]), type 2 (32 DU), and type 3 (45 DU) Sabin IPV were similar to those of the OPV and cIPV control groups. CLINICAL TRIALS REGISTRATION NCT01056705.

Hepatitis B virus precore protein augments genetic immunizations of the truncated hepatitis C virus core in BALB/c mice

DNA immunization has been used to induce either humoral or cellular immune responses against many antigens, including hepatitis C virus (HCV). In addition, DNA immunizations can be enhanced or modulated at the nucleotide level. Genetic immunizations were examined in BALB/c mice through the use of plasmids and chimeric DNA constructs encoding HCV core proteins and hepatitis B virus (HBV) precore (preC) regions. Plasmids encoding the truncated HCV core induced potent humoral and cellular responses to HCV; pcDNA3.0A‐C154 produced a stronger antibody response than pcDNA3.0A‐C191 (P < 0.01) and pcDNA3.0A‐C69 (P < 0.05). HBV preC enhanced the humoral and cellular immune responses of BALB/c mice to HCV; however, pcDNA3.0A‐C69preC resulted in a weak cytotoxic T lymphocyte (CTL) response. In addition, the humoral and cellular immune responses to HCV of groups immunized with pcDNA3.0A‐C154preC and pcDNA3.0A‐C191preC plasmids were higher than those of groups immunized with pcDNA3.0A‐C154 and pcDNA3.0A‐C191. In vivo CTL responses verified that mice immunized with preC core fused DNAs showed significantly high specific lysis compared with mice immunized with HCV cores only (P < 0.01). In our study, pcDNA3.0A‐C154preC led to the highest immune response among all DNA constructs. Conclusion: DNA that encodes truncated HCV core proteins may lead to increased immune responses in vivo, and these responses may be enhanced by HBV preC. (HEPATOLOGY 2007.)

Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine.

The World Health Organization has recommended that a Sabin inactivated polio vaccine (IPV) should gradually and synchronously replace oral polio vaccines for routine immunizations because its benefits in eliminating vaccine-associated paralytic poliomyelitis have been reported in different phases of clinical trials. It is also considered important to explore new tetravalent diphtheria, tetanus, and acellular pertussis-Sabin IPV (DTaP-sIPV) candidate vaccines for possible use in developing countries. In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced. The dynamic profiles of the antibody responses to each of the separate antigenic components and serotypes of Sabin IPV were determined and their corresponding geometric mean titers were similar to those generated by the tetravalent diphtheria, tetanus, and acellular pertussis-conventional IPV (DTaP-cIPV), the tetravalent diphtheria, tetanus, and acellular pertussis (DTaP), and Sabin IPV vaccines in the control groups. This implies that protective immunogenic effects are conferred by this combined tetravalent formulation.

Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats

ABSTRACT Objective: The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats.

Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses

Background A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Methods Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. Results All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Conclusions Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. Clinical Trials Registration NCT01056705.

The ERAP gene is associated with HCV chronic infection in a Chinese Han population

Endoplasmic reticulum aminopeptidases (ERAPs), ERAP1 and ERAP2, are critical components in the antigen-presentation system and are specialized to produce optimal-sized peptides for HLA I binding. ERAP gene polymorphisms have been correlated with HLA-associated diseases. To investigate the association between ERAP gene polymorphisms and HCV chronic infection, a TaqMan assay was used to genotype 4 SNPs (rs27044, rs30187, rs26618 and rs26653) in ERAP1 and 2 SNPs (rs2248374 and rs2549782) in ERAP2 genes in 376 Chinese Han HCV chronic infections and 324 healthy Chinese Han controls. The allelic distribution of rs26618 in the ERAP1 gene and rs2248374 in ERAP2 gene were both significantly different in case and control groups. The C-allele of rs26618 had an increased HCV chronicity risk compared with the T-allele (P=.025, OR=1.318, 95%CI: 1.035-1.677), and the same effect was found in A-allele of rs2248374 compared with G-allele (P=0.046, OR=1.244, 95%CI: 1.004-1.540). There were notable differences in the genotype distribution in analysis using the dominant genetic model in rs26618 (CC+CT vs. TT; P=0.007, OR=1.473, 95%CI: 1.091-1.989) and recessive genetic model in rs2248374 (AA vs. AG+GG; P=0.003, OR=1.548, 95%CI: 1.026-2.335). In addition, rs26618 and rs2248374-genotype combination played noteable effects on the clinical parameters. These results indicated that the ERAP gene may play a critical role in HCV chronicity in this Chinese Han population.

Experimental infection characteristics of Bordetella pertussis via aerosol challenge on rhesus macaques

The effect of aerosol challenge of rhesus macaques with Bordetella pertussis and the feasibility of using rhesus monkeys as an animal model for pertussis infection were evaluated in this study. Four 1-year old rhesus macaques were aerosol challenged with B. pertussis at the concentration of 105 CFU/mL for 30 min (group 1) or 60 min (group 2). Rectal temperature was found slightly increased at days 3 and 5 and returned to baseline levels at day 21 after challenge. White blood cell counts peaked at day 7, with a 4.7~6.1-fold increase and returned to baseline levels at day 45. Bacteria colonization of nasopharyngeal swabs was observed, and the number of colonies was gradually increased and peaked at day 14, reaching 5.4-8.1 × 106/mL. The seroconversion rate of anti-pertussis toxin (PT), pertactin (PRN), and filamentous hemagglutinin(FHA) antibodies was 100%, with an increase in geometric mean titers after challenge. Analysis of cytokines revealed that the levels of cytokines including IL-2, IL-6, IL-8, IL-10, IL-17A, IL-13, IL-12, and IL-18 were significantly increased at days 5 to 14 in group 2. These results demonstrate that the characteristic of pertussis infection in infant rhesus macaque was similar as in human beings, which provide a clue to using infant rhesus macaque as a candidate model for pertussis infection in the future studies

A simple and safe antibody neutralization assay based on polio pseudoviruses

ABSTRACT The evaluation of the immunogenicity of Sabin strain based Inactivated Poliovirus Vaccines (sIPV) necessitates the use of wild strains in neutralization assays to assess the potential cross-reactivity of antibodies. The live virus strains including wild and Sabin strains must be handled in level 3 biocontainment laboratories. To develop an alternative assay without the use of a live virus, we constructed Mahoney, MEF-1, and Saukett pseudovirions by inserting luciferase reporter genes into intact capsid proteins. Afterward, we developed a pseudovirus-based neutralization test (pNT) and evaluated for the specificity and reproducibility. We tested serum samples from a clinical trial on sIPV vaccines by pNT and compared the results with those obtained from conventional neutralization tests (cNT). A strong correlation was observed between two methods, with the correlation coefficients of all three types of IPV vaccines being greater than 0.82 (p < 0.0001). The Geometric Mean Titer (GMT) values obtained by pNT were approximately four times higher than that by cNT, revealing the better sensitivity of pNT. In conclusion, pNT is a safe, rapid and sensitive quantitative assay with the potential of being an alternative for the evaluation of the potency of polio vaccines.

Genetic polymorphisms in the TERT gene and susceptibility to non-small cell lung cancer in a Chinese Han population

Background Recent studies have revealed that the TERT gene plays crucial roles in cancer initiation and development. Genome-wide analysis studies and case-control studies have demonstrated that polymorphisms in the TERT gene are associated with various cancers. Materials and methods In the current study, we analyzed the associations of eight single nucleotide polymorphisms (SNPs) in the TERT gene with non-small cell lung cancer (NSCLC) in a Chinese Han population. A total of 467 NSCLC patients and 526 healthy individuals were recruited for SNP genotyping using a TaqMan assay. Results Our results revealed that the allelic frequencies of rs2853677 and rs2853691 were significantly different between the NSCLC and control groups (P=0.004 and 0.001, respectively). Moreover, the T allele of rs2853677 and the A allele of rs2853691 might be the protective factors against NSCLC (OR=0.766; 95%CI: 0.639–0.918 and OR=0.714; 95%CI: 0.584–0.875, respectively). Additionally, stratified association analysis of the eight SNPs with the different pathological NSCLC stages (I+II and III+IV) and different pathological types (adenocarcinoma and squamous cell carcinoma) revealed that none of the SNPs were significantly different between patients with different pathological stages and pathological types. Conclusion Our results indicated that rs2853677 and rs2853691 in the TERT gene might be associated with NSCLC in this Chinese Han population.