目的 LNP(linear-nonlinear-Poisson)模型很好地解译了神经元的响应过程,其重要环节之一是线性滤波器的提取。针对传统i STAC(information-theoretic spike-triggered average and covariance)算法运用于LNP模型时的神经元特性表征不足...目的 LNP(linear-nonlinear-Poisson)模型很好地解译了神经元的响应过程,其重要环节之一是线性滤波器的提取。针对传统i STAC(information-theoretic spike-triggered average and covariance)算法运用于LNP模型时的神经元特性表征不足、运动特征提取效果不佳等问题,特别是在处理低维度刺激问题时,提出了一种改进的i STAC神经元滤波特征提取算法。方法引入非触发刺激的统计量,从而更加准确地构建神经元滤波特征子空间的目标函数,同时增强系统的抗噪能力;采用变尺度法最大化目标函数,从而优化解空间,提升算法的收敛速率。结果不同非线性条件下对线性滤波器的恢复实验结果表明,新算法相较于传统i STAC算法在高维度刺激时保持较好的表征特性,在刺激维度小于6 500时有明显改善,且总体上优于STA(spike-triggered average)和STC(spike-triggered covariance)算法。结论提出的新算法适用范围更广,鲁棒性更强,能够运用于建立完整的基于视觉特性的视频运动特征提取模型。展开更多
Latent varicella-zoster virus(VZV)may be reactivated to cause herpes zoster,which affects one in three people during their lifetime.The currently available subunit vaccine Shingrix^(TM) is superior to the attenuated v...Latent varicella-zoster virus(VZV)may be reactivated to cause herpes zoster,which affects one in three people during their lifetime.The currently available subunit vaccine Shingrix^(TM) is superior to the attenuated vaccine Zostavax®in terms of both safety and efficacy,but the supply of its key adjuvant component QS21 is limited.With ionizable lipid nanoparticles(LNPs)that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers,and oligodeoxynucleotides containing CpG motifs(CpG ODNs)approved by the FDA for a subunit hepatitis B vaccine as immunostimulators,we developed a LNP vaccine encapsulating VZV-glycoprotein E(gE)and CpG ODN,and compared its immunogenicity with Shingrix^(TM) in C57BL/6J mice.The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to Shingrix^(TM) as determined by enzymelinked immunosorbent assay(ELISA).Most importantly,the LNP vaccine induced comparable levels of cellmediated immunity(CMI)that plays decisive roles in the efficacy of zoster vaccines to Shingrix^(TM) in a VZVprimed mouse model that was adopted for preclinical studies of Shingrix^(TM) .Number of IL-2 and IFN-γsecreting splenocytes and proportion of T helper 1(Th1)cytokine-expressing CD4^(+)T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of Shingrix^(TM) boosted mice.All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities,indicating the potential of LNP-CpGadjuvanted VZV-gE as a more cost-effective zoster vaccine.展开更多
We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOM...We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from <em>C</em>. <em>muridarum</em> elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to <em>C</em>. <em>muridarum</em> nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P < 0.001) and <em>C</em>. <em>muridarum</em> EBs (P < 0.001), when compared to the adjuvant alone group. Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA) + LNP were higher as compared to the MPLA + DDA group (P < 0.001) except for (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + DDA) vs (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + LNP) for both <em>C</em>. <em>muridarum</em> EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-<em>γ</em>/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with <em>Chlamydia</em> antigens also showed protection from <em>C</em>. <em>muridarum</em> challenge, by reduction in bacterial shedding for all groups (P < 0.003) compared to shedding from the adjuvant control. Both vaccine formulations generated robust immunological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.展开更多
基金supported by the Major Science and Technology Special Projects of Yunnan Province,China (202002AA100009)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-JKCS-012)+5 种基金the Special Biomedicine Projects of Yunnan Province (202102AA310035)National Natural Science Foundation of China (82104130)Fundamental Research Funds for the Central Universities (3332021072)the Basic Research Projects of Yunnan Province (202101AU070176, 202101AT070286)the Funds for the Training of High-level Health Technical Personnel in Yunnan Province(grant number H-2019063)the Funds for High-level Scientific and Technological Talents Selection Special Project of Yunnan Province(202205AC160015)
文摘Latent varicella-zoster virus(VZV)may be reactivated to cause herpes zoster,which affects one in three people during their lifetime.The currently available subunit vaccine Shingrix^(TM) is superior to the attenuated vaccine Zostavax®in terms of both safety and efficacy,but the supply of its key adjuvant component QS21 is limited.With ionizable lipid nanoparticles(LNPs)that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers,and oligodeoxynucleotides containing CpG motifs(CpG ODNs)approved by the FDA for a subunit hepatitis B vaccine as immunostimulators,we developed a LNP vaccine encapsulating VZV-glycoprotein E(gE)and CpG ODN,and compared its immunogenicity with Shingrix^(TM) in C57BL/6J mice.The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to Shingrix^(TM) as determined by enzymelinked immunosorbent assay(ELISA).Most importantly,the LNP vaccine induced comparable levels of cellmediated immunity(CMI)that plays decisive roles in the efficacy of zoster vaccines to Shingrix^(TM) in a VZVprimed mouse model that was adopted for preclinical studies of Shingrix^(TM) .Number of IL-2 and IFN-γsecreting splenocytes and proportion of T helper 1(Th1)cytokine-expressing CD4^(+)T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of Shingrix^(TM) boosted mice.All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities,indicating the potential of LNP-CpGadjuvanted VZV-gE as a more cost-effective zoster vaccine.
文摘We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from <em>C</em>. <em>muridarum</em> elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to <em>C</em>. <em>muridarum</em> nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P < 0.001) and <em>C</em>. <em>muridarum</em> EBs (P < 0.001), when compared to the adjuvant alone group. Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA) + LNP were higher as compared to the MPLA + DDA group (P < 0.001) except for (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + DDA) vs (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + LNP) for both <em>C</em>. <em>muridarum</em> EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-<em>γ</em>/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with <em>Chlamydia</em> antigens also showed protection from <em>C</em>. <em>muridarum</em> challenge, by reduction in bacterial shedding for all groups (P < 0.003) compared to shedding from the adjuvant control. Both vaccine formulations generated robust immunological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.
