Jaap Goudsmit

..Using this process as a model, the general requirements for development of safe and efficacious monoclonal antibody alternatives to currently used polyclonal serum products are discussed...

..From in vitro studies it has become clear that these drugs can affect specific genes, as well as have an effect upon the total transcriptome...

..Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome...

..These results demonstrate that the human MAb cocktail of CR57 and CR4098 is a safe and efficacious alternative to RIG in rabies postexposure prophylaxis...

..Our results show the ability of rAd35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule without impairing the B-cell response...

..Such rAd35 vectors thus expand the utility of rAd35 vaccine carriers for the development of vaccines against, for example, malaria, AIDS and tuberculosis...

..CS alone. With these results we report for the first time the feasibility of using an AlPO(4) adjuvant to increase the potency of a live adenovirus serotype 35-based vaccine...

..SIVGag vaccine. These data demonstrate the potential of a replication deficient human group D adenoviral vector for vaccination purposes...

..These results unify conflicting reports on the relative importance of CD4 versus CD8 T-cell responses in protection and emphasize the key role of IFN-gamma...

..The obtained specificities expand the set of human anti-RV antibodies eligible for inclusion in an antibody cocktail aimed for use in rabies post-exposure prophylaxis...

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..CS or possibly another adenovector of a distinct serotype, induces a complex immune response that is required for protection against malaria, and is thus a highly promising approach for pediatric vaccination...

..The complete set of SARS-CoV MAbs described here may be useful for diagnosis, chemoprophylaxis, and therapy of SARS-CoV infection and disease...

..We therefore conclude that the Ad11-based vector represents a novel and useful candidate gene transfer vehicle for vaccination and gene therapy...

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..Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes...

..Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection...

..This review will give an overview of vaccines under development and summarize current data on E-protein antigenicity that could aid in the design of next generation WNV vaccines...

..We concluded that the assay is suitable for the measurement of polyclonal and monoclonal rabies neutralizing antibodies in clinical serum samples...

..These results justify further preclinical evaluation of broadly neutralizing mAbs against influenza virus for the prevention and treatment of influenza virus infections...

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..We thus conclude that, for ex vivo vaccination, Ad5.Fib35 shows promise as vector for loading of DC but is unable to circumvent anti-Ad5 immunity limiting its in vivo utility...

..Our results show that rational design of antigens is warranted for further development of malaria vaccines...

..This review provides an overview of heterologous prime-boost vaccination modalities currently in development for the 'big three' poverty-related diseases and emphasizes the need for innovative vaccination approaches...

..C6 cells throughout a standard purification process. Because of its specifications, we anticipate that the assay can have broad applicability to biologics other than adenoviral vectors produced on PER.C6 cells...

..SIVgag vaccine as compared with rAd35.SIVgag exposed dendritic cells from wild-type littermates. It was concluded that MYII mice represent an interesting preclinical model to evaluate potency and safety of rAd35 vectors...

..Here we report the latest efficacy data for a representative antibody of this novel class...

..Ad35 is less prone to neutralization than Ad5, encouraging the further development of Ad35 for vaccination against HIV...

..We further demonstrate that transduction with Ad35 is not hampered by preexisting Ad5 immunity and that Ad35 efficiently infects dendritic cells, smooth muscle cells, and synoviocytes, in contrast to Ad5...

..CS/Ad26.CS vaccine at a later age, to induce lasting protection against malaria for which the Th1 response and immune memory is required...

..Antibody titers were in agreement with total antibody responses to the whole CS protein. Due to its simplicity and high performance, the ELISA is an easy and rapid method for assessment of pre-erythrocyte malaria vaccines based on CS...

..Plasma viral load testing can ensure a more efficient allocation of antiretroviral therapy but only when applied to a strategy of active case finding in the community...

..C6((R)) cell cultures. The RP-HPLC assay selectivity allows for the simultaneous identification and quantification of HA(1) from influenza A and B strains in the yearly revised trivalent vaccines for epidemic outbreaks...

..Combinations of virus-neutralizing, noncompeting mAbs may have these properties...

..If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak...

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..Based on our findings, we are exploring PER.C6(®) as an interesting platform for large-scale production of poliovirus at low costs, potentially providing the basis for global supply of an affordable IPV...

..The data generated in this animal model show that administration of a human monoclonal antibody might offer a feasible and effective prophylaxis for the control of human SARS coronavirus infection...

..Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years...

..Based on simplicity, speed, high throughput, sensitivity, and robustness, we propose a qualified assay in which Ad neutralization is monitored by luciferase reporter gene expression...

..The AML reactivity combined with the restricted expression on normal cells identifies CLL-1 as a novel potential target for AML treatment...

..An immunogen that elicits broadly reactive neutralizing antibodies, however, has yet to be developed...

..In a hospital-based setting in resource-poor environments this ensures an efficient treatment allocation...

..In summary, for prognosis, the markers CD4 count, HIV-1 RNA load, and HIV-1 phenotype (at a high CD4 count) are equally important, and the genetic cofactors considered are of no use...

..These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines...

..One subject demonstrated a window period of at least 204 days, combined with a high preseroconversion viral load and no decline of CD4 T cells over a follow-up period of at least 3 years...

..Unlike HIV-1, HBV, or HCV infection, HHV-8 infection is uncommon in Amsterdam drug users, as is HHV-8 transmission through IDU...

..Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens...

..Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity...

..The number of long-term survivors is substantially increased only when vaccination is initiated early in an AIDS epidemic, however...

..Thus, i.m. vaccination can overcome immune compartmentalization and generate robust mucosal CD8(+) T lymphocyte memory. These data demonstrate that the systemic and mucosal immune systems are highly coordinated following vaccination...

..Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation...

..Half of the 10 assessed responded in the ELISpot assay under stringent criteria, which informed the sample size for a DNA-NYVAC-C comparison to NYVAC-C alone...

..04; 95% CI, 1.0-1.07). Measurement of viral load after approximately 7 days provided the most accurate measure of the degree of viral suppression induced by a given drug regimen...

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..Finally, we show that a low-affinity antibody may only detect high expression levels of a surface marker while failing to detect lower expression levels of this molecule, which may lead to a false interpretation of antibody specificity...

..The possibility that viruses with a C' envelope have a biological advantage over the viruses with a C" envelope should be further investigated in biological and epidemiological studies...

..These studies suggest a potential strategy for engineering novel Ad5 vectors to evade dominant Ad5-specific NAbs...

..Recent safety, immunogenicity, and efficacy trials in the US and Africa are presented, as well as plans for the development of a multi-antigen vaccine...

..Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both humoral and cellular Ad5-specific immune responses...

..These experiments demonstrate that phage antibody selection in combination with affinity chromatography and mass spectrometry can be exploited successfully to identify novel antibody target molecules on malignant cells...

..These results indicate that even though R5 subtype C viruses are restrictive for virus replication, the R5-to-X4 phenotype switch can occur and does so in a manner similar to that of subtype B viruses...

..Longitudinal serum samples from 19 AIDS-Kaposi's sarcoma patients, ranging from 2 years before KS till 2 years after KS diagnosis were tested. No correlation was found between viral load and progression to KS, or disease stage...

..In vitro exposure of RV to the combination of CR57 and CR4098 yielded no escape mutants. In conclusion, a novel combination of human MAbs was discovered suitable to replace RIG...

..These results demonstrate the sequential accumulation of CTL escape in a patient during disease progression, indicating that multiple combinations of T-cell epitopes are required to control viremia...

..This suggests that loss of T-cell reactivity may not be directly linked to HIV-specific CD4(+) T-cell responses but that increased viremia after CTL escape may influence CD4(+) T-helper responses...

..These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world...

..The increased T-cell responses induced by the combination of Ad35.CS and RTS,S/AS01B are sustained for at least 6 months postvaccination and may translate to improved and more durable protection against P. falciparum infection in humans...

..Measuring the HIV-1 burden from whole blood dried on filter paper provides a suitable alternative for low-technology settings with limited access to refrigeration, as can be found in sub-Saharan Africa...

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..GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine...

..Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy...

..Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes...

..To coordinate preclinical toxicology studies under GLP conditions and prepare IND applications to support the initiation of phase I and phase II clinical trials...