Elawati Soenawan

Novartis Vaccines, Cambridge, Massachusetts, United States

Are you Elawati Soenawan?

Claim your profile

Publications (10)42.38 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although alum is the most commonly used vaccine adjuvant, it has some limitations for use with the next generation recombinant antigens. We explored the use of alternative adjuvant formulations (poly lactide co-glycolide (PLG) microparticles, MF59 emulsion, CAP and l-tyrosine suspension) in comparison with five different vaccine antigens—namely, diphtheria toxoid (DT), tetanus toxoid (TT), HBsAg, Men C conjugate and MB1. The results indicated that although alum was optimal for bacterial toxoid based vaccines, it was not highly potent for MB1, Men C or HBsAg antigens. MF59 emulsion stood out as a good alternative to alum for TT, HBsAg, MB1 and Men C vaccines. On the other hand l-tyrosine suspension and CAP did not enhance immune responses over alum with most antigens. PLG microparticles were comparable or better than alum with both MB1 and Men C conjugate vaccine. The study indicates that it is possible to replace alum with other adjuvant formulations like MF59 and PLG and maintain and/or improve immune responses with some vaccine antigens.
    Vaccine 04/2006; · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Monophosphoryl lipid A (MPL) and the synthetic LPS mimetic RC529, encapsulated in poly(lactide-co-glycolide) (PLG) microparticles, were evaluated as immune potentiators in the presence of either HIV-1 gp120 protein or antigen from Neisseria meningitidis serotype B (Men B). The immunogenicity of these formulations was evaluated in mice and compared to CpG containing oligonucleotide. This work was done as part of an ongoing effort to enhance the potency of vaccine candidates against HIV and Men B. Microparticles were made by a solvent evaporation method. Blank microparticles as well as microparticles with encapsulated MPL or RC529 were made using the PLG polymer RG503 and the ionic surfactant Dioctylsulfosuccinate by the water-in-oil-in-water emulsion technique. Antigens from HIV-1 and Men B were adsorbed on the surface of these anionic microparticles and the final formulations characterized for protein loading, release, and integrity. The formulations were then tested in mice for their ability to elicit antibodies and bactericidal activity in comparison with CpG containing oligonucleotide. We have found that adding soluble immune potentiators to Men B antigen formulated on PLG microparticles significantly enhanced the immune response to a level comparable to that obtained using CpG. In a separate study, we found that encapsulating MPL or RC529 in PLG microparticles further enhanced the response in comparison to soluble CpG, which is our control group. Similarly, adding soluble immune potentiators to gp120 antigen formulated on PLG microparticles resulted in a significant enhancement of the immune response. Moreover, delivering MPL or RC529 encapsulated in PLG microparticles with gp120 adsorbed on PLG microparticles, resulted in even further enhancement of serum titers over those obtained with soluble immune potentiators. These titers were comparable to or greater than those obtained with soluble CpG, the control group. This effect was observed for both antigens regardless of whether or not the immune potentiator and the antigen were used with the same or with separate particles. In conclusion, the advantages of encapsulating MPL and RC529 lie not only in the enhanced immune response they elicit, but also in the convenience of handling these relatively insoluble compounds, and flexibility in vaccine design. The fact that MPL and RC529 are readily soluble in methylene chloride used for the manufacturing of PLG microparticles makes it easy to avoid solubility issues. Moreover, formulating antigen and immune potentiator with the same particle offers an attractive approach to vaccine delivery.
    Journal of Controlled Release 03/2006; 110(3):566-73. · 7.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasmid DNA is currently being considered for immunization as an alternative approach to protein-based vaccines. The prevailing opinion is that the linear and open-circular forms of plasmid DNA are less effective than the supercoiled isoform in inducing immune responses. However, it can be argued that the plasmid is likely to be nicked and relaxed during its transport into the nucleus, regardless of the level of supercoiling present. This article investigates the validity of the recommendations regarding supercoiling requirements for optimal efficiency of DNA vaccines. Some studies appear to be consistent with the notion that cell transfection with plasmids is better with the supercoiled than the relaxed open-circular isoform. Other studies have shown that there is a minimum limit of supercoiled plasmid that needs to be present for potent in vivo responses to DNA vaccines, with the limit being reported to be >70% in one study. However, other data indicate that gene transfer is not significantly affected by the level of supercoiling of the gene, and cationic lipids and microparticles can be used to deliver both isoforms without significant loss of efficiency in vivo.To further address this issue, we evaluated the in vitro and in vivo potency of DNA plasmids encoding the HIV proteins, gp140 env and p55 gag. The in vitro results showed no relationship between the degree of supercoiling and cellular transfection efficiency. Similarly, the antibody titers measured in mice immunized with fully relaxed open-circle plasmids were not significantly different from responses elicited with supercoiled plasmid. However, linearized DNA was ineffective.Based on the findings of ourselves and others that the relaxed open-circular form of a plasmid DNA is no less efficient in transfecting cells or in eliciting antibody responses than its supercoiled form, we propose that it is possible to lower the requirement for a high percentage of supercoiled plasmid in a DNA vaccine formulation.
    American Journal of Drug Delivery 12/2005; 4(4):195-199.
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is an urgent need to develop vaccines that can elicit immunological memory responses against HIV. Using the rhesus macaque model and a combination of intranasal (IN) and parenteral immunizations with DNA or protein adsorbed to microparticles or mixed with mucosal adjuvants we sought to induce anti-HIV memory-type immune responses in both the mucosal and systemic compartments. Prime/boost immunizations were performed through five IN immunizations alone with HIV-env oligomeric gp140 (Ogp140) or HIV-gag-p24 mixed with Escherichia coli heat labile-derived mutant adjuvants or two parenteral immunizations with DNA encoding HIV-env or -gag adsorbed to microparticles followed by three IN immunizations with p24 gag protein and the mutant adjuvants. Both modes of immunizations induced anti-gp140 plasma and vaginal IgG and IgA as well as interferon (IFN)-gamma secreting peripheral blood mononuclear cells (PBMC) after HIV-env and -gag peptide restimulation. After a resting period of 4 months, when the levels of humoral and cellular responses had decreased, intramuscular (IM) booster immunizations with p55-gag protein adsorbed to microparticles and Ogp140 in MF59 oil in water emulsion significantly enhanced anti-HIV plasma and vaginal antibody, as well as peripheral blood IFN-gamma responses in all groups of vaccinated macaques. Importantly, plasma neutralization activity against both homologous and heterologous HIV strains was observed in all groups following the IM booster immunizations with protein. These findings show that IN priming alone or combinations of parenteral and IN immunizations followed by IM booster immunizations hold promise to significantly enhance mucosal and systemic memory-type immune responses against HIV-1 antigens.
    AIDS Research and Human Retroviruses 12/2004; 20(11):1269-81. · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To understand the mechanisms involved in maintaining long-term immunological memory following mucosal immunizations, we determined the quality of serum hapten-specific immunoglobulins (Ig) and localized Ig-secreting cells (SC) of various isotypes in acute, persistent/resting memory and effector memory phases following oral versus intra-muscular (IM) immunizations. In the acute phase, both oral and IM immunizations induced high avidity Ig. However, in the persistent/resting memory phase, oral immunizations induced low avidity Ig while IM immunizations induced high avidity Ig. Following oral immunizations, in the persistent/resting memory phase, hapten-specific IgM titers in serum and IgM-SC in bone marrow (BM) dominated the immune response, suggesting an important role for IgM in the maintenance of memory.
    Vaccine 04/2004; 22(11-12):1553-63. · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The adsorption behavior of model proteins onto anionic poly(lactide-co-glycolide) (PLG) microparticles was evaluated. PLG microparticles were prepared by a w/o/w solvent evaporation process in the presence of the anionic surfactant dioctyl sodium sulfosuccinate (DSS). The effect of surfactant concentration and adsorption conditions on the adsorption efficiency and release rates in vitro was also studied. Subsequently, the microparticle formulation was tested to evaluate the efficacy of anionic microparticles as delivery systems for recombinant antigens from Neisseria meningitides type B (Men B), with and without CpG adjuvant. Protein (antigen) binding to anionic PLG microparticles was influenced by both electrostatic interaction and by other mechanisms, including hydrophobic attraction. The Men B antigens adsorbed efficiently onto anionic PLG microparticles and, following immunization in mice, induced potent enzyme-linked immunosorbent assay (ELISA) and serum bactericidal activity in comparison to alum-adsorbed formulations. These Men B antigens represent an attractive approach for vaccine development.
    Journal of Pharmaceutical Sciences 03/2004; 93(2):273-82. · 3.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is estimated that Helicobacter pylori infects the stomachs of over 50% of the world's population and if not treated may cause chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and gastric B-cell lymphoma. The aim of this study was to enhance the mucosal and systemic immune responses against the H. pylori antigens cytotoxin-associated gene A (CagA) and neutrophil-activating protein (NAP), through combinations of mucosal and systemic immunizations in female BALB/c mice. We found that oral or intranasal (i.n.) followed by i.m. immunizations induced significantly higher serum titres against NAP and CagA compared to i.n. alone, oral alone, i.m. alone, i.m. followed by i.n. or i.m. followed by oral immunizations. However, only oral followed by i.m. immunizations induced anti-NAP antibody-secreting cells in the stomach. Moreover, mucosal immunizations alone or in combination with i.m., but not i.m. immunizations alone, induced mucosal immunoglobulin A (IgA) responses in faeces. Any single route or combination of immunization routes with NAP and CagA preferentially induced antigen-specific splenic interleukin-4-secreting cells and far fewer interferon-gamma-secreting cells in the spleen. Moreover, i.n. immunizations alone or in combination with i.m. immunizations induced predominantly serum IgG1 and far less serum IgG2a. Importantly, we found that while both i.n. and i.m. recall immunizations induced similar levels of serum antibody responses, mucosal IgA responses in faeces were only achieved through i.n. recall immunization. Collectively, our data show that mucosal followed by systemic immunization significantly enhanced local and systemic immune responses and that i.n. recall immunization is required to induce both mucosal and systemic memory type responses.
    Immunology 10/2003; 110(1):86-94. · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cationic PLG microparticles with adsorbed DNA have previously been shown to efficiently target antigen presenting cells in vivo for generating higher immune responses in comparison to naked DNA. In this study we tried to establish the role of surfactant (CTAB) concentration on the physical behavior of these formulations. Cationic PLG microparticle formulations with adsorbed DNA were prepared using a solvent evaporation technique. Formulations with varying CTAB concentrations and a fixed DNA load were prepared. The loading efficiency and 24 h DNA release was evaluated for each formulation. Select formulations were tested in vivo. Higher CTAB concentration correlated with higher DNA binding efficiency on the microparticles and lower in vitro release rates. Surprisingly though, the in vivo performance of formulations with varying CTAB concentration was comparable to one another. Cationic PLG microparticles with adsorbed DNA, as described here, offer a robust way of enhancing in vivo responses to plasmid DNA.
    Pharmaceutical Research 03/2003; 20(2):247-51. · 4.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ability of 2 mutants of heat-labile Escherichia coli enterotoxin (LTK63 and LTR72) to enhance the immunogenicity of 2 protein polysaccharide conjugate vaccines, Neisseria meningitidis group C (MenC) and Haemophilus influenzae type B (Hib), both of which are conjugated to the nontoxic mutant of diphtheria toxin (CRM197), after intranasal (inl) immunization in mice was evaluated. In addition, the question of whether combining both vaccines in a single formulation with heat-labile E. coli enterotoxin mutants reduced the response to either vaccine was investigated. The results showed that potent serum antibody responses against MenC and Hib could be elicited by inl immunization in combination with the mucosal adjuvants. Moreover, IgA mucosal responses were induced only in animals immunized through the inl route. Finally, the coadministration of 2 conjugate vaccines simultaneously did not adversely affect the responses against either. These studies support the rationale for developing mucosal vaccines, based on combining protein polysaccharide conjugates with heat-labile E. coli enterotoxin mutants, for infants and young children.
    The Journal of Infectious Diseases 12/2002; 186(9):1358-61. · 5.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel cationic emulsion was developed to adsorb plasmid DNA and improve intracellular delivery of plasmid DNA upon immunization. The emulsion developed, had a highly uniform particle and charge distribution. Based on observations with cationic microparticles, the cationic emulsion was evaluated in vivo in mice and rabbits with a model HIV-1 pCMVp55 gag DNA. In both these species, the cationic emulsion engendered higher antibody responses than those obtained with naked DNA. The cationic emulsion also maintained the cellular responses seen with naked DNA at the same doses.
    Journal of Controlled Release 03/2002; · 7.63 Impact Factor