Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report

BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

Carbohydrate-associated epitope-based anti-cancer drugs and vaccines

RP215 is one of the three thousand monoclonal antibodies (Mabs) which were generated against the OC-3-VGH ovarian cancer cell line. RP215 was shown to react with a carbohydrate-associated epitope located specifically on glycoproteins, known as CA215, from cancer cells. Further molecular analysis by matrix adsorption laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that CA215 consists mainly of immunoglobulin super-family (IgSF) proteins, including immunoglobulins, T-cell receptors, and cell adhesion molecules, as well as several other unrelated proteins. Peptide mappings and glycoanalysis were performed with CA215 and revealed high-mannose and complex bisecting structures with terminal sialic acid in N-glycans. As many as ten O-glycans, which are structurally similar to those of mucins, were also identified. In addition, two additional O-linked glycans were exclusively detected in cancerous immunoglobulins but not in normal B cell-derived immunoglobulins. Immunizations of mice with purified CA215 resulted in the predominant generation of RP215-related Mabs, indicating the immunodominance of this carbohydrate-associated epitope. Anti-idiotype (anti-id) Mabs of RP215, which were generated in the rat, were shown to contain the internal images of the carbohydrate-associated epitope. Following immunizations of these anti-id Mabs in mice, the resulting anti-anti-id (Ab3) responses in mice were found to be immunologically similar to that of RP215. Judging from these observations, anti-id Mabs, which carry the internal image of the RP215-specific epitope, may be suitable candidates for anticancer vaccine development in humans.

表位结构指导免疫优势转移的HPV交叉疫苗的理性设计

In vaccine development,broadly or cross-type neutralizing antibodies(bnAbs or cnAbs)are frequently targeted to enhance protection.Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies.However,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated.In this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and HPV11.This nAb exhibited a marked preference for HPV6,demonstrating superior binding activity to virus-like particles(VLPs)and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum(90%vs.31%).Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex,we delineated the epitope as spanning four segments of amino acids(Phe42-Ala47,Gly172-Asp173,Glu255-Val275,and Val337-Tyr351)on the L1 surface loops.Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1.Substituting Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to 13H5.By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI VLPs.Remarkably,the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates.This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

Multiobjective optimization using an immunodominance and clonal selection inspired algorithm

Based on the mechanisms of immunodominance and clonal selection theory, we propose a new multiobjective optimization algorithm, immune dominance clonal multiobjective algorithm （IDCMA）. IDCMA is unique in that its fitness values of current dominated individuals are assigned as the values of a custom distance measure, termed as Ab-Ab affinity, between the dominated individuals and one of the nondominated individuals found so far. According to the values of Ab-Ab affinity, all dominated individuals （antibodies） are divided into two kinds, subdominant antibodies and cryptic antibodies. Moreover, local search only applies to the subdominant antibodies, while the cryptic antibodies are redundant and have no function during local search, but they can become subdominant （active） antibodies during the subsequent evolution. Furthermore, a new immune operation, clonal proliferation is provided to enhance local search. Using the clonal proliferation operation, IDCMA reproduces individuals and selects their improved maturated progenies after local search, so single individuals can exploit their surrounding space effectively and the newcomers yield a broader exploration of the search space. The performance comparison of IDCMA with MISA, NSGA-Ⅱ, SPEA, PAES, NSGA, VEGA, NPGA, and HLGA in solving six well-known multiobjective function optimization problems and nine multiobjective 0/1 knapsack problems shows that IDCMA has a good performance in converging to approximate Pareto-optimal fronts with a good distribution.

Optimization of virtual machine placement based on constrained immune memory and immunodominance clone in IaaS cloud mode equipment training

In infrastructure as a service(IaaS)cloud mode equipment simulated training,to keep the resource utilization ratio in a rational high level,improve the training effect and reduce the system running cost,the problem of training virtual machine(TVM)placement needs to be resolved first.We make analysis to the problem and give the mathematical formulation to the problem.Then,we figure out the principle and target of the TVM placement.Based on above analysis,we propose a constrained immune memory and immunodominance clone(CIMIC)TVM placement optimization algorithm.By reverse optimization of the initial antibody population,the searching range is reduced.The common antibody population and the immunodominance antibody population evolve simultaneously,which realizes the simultaneous progressing of global searching and local searching of solutions.Further,local optimal is avoided by this means.Memory antibody makes ful use of the unfeasible solutions and the diversity of antibody population is maintained.The constraint information of the problem is utilized to improve the optimization effect.Experiment results show that the CIMIC algorithm improves the overall optimization effect of TVM placement,reduces the server number and improves the resource utilization and system stability.