lipid-a and aluminum-phosphate

A new hepatitis B vaccine (FENDrix, GlaxoSmithKline Biologicals) containing as active substance 20 microg of recombinant hepatitis B virus surface antigen produced in Saccharomyces cerevisiae has recently been licensed in Europe. It is prepared with a novel adjuvant system: aluminum phosphate and 3-O-desacyl-4 -monophosphoryl lipid A. It is intended for use in adults from the age of 15 years onwards for active immunization against hepatitis B virus infection for patients with renal insufficiency (including prehemodialysis and hemodialysis patients). It is applied in a four-dose scheme: day 0, month 1, 2 and 6 after day 0. Due to the improved adjuvant system it induces higher antibody concentrations that reach protective levels in a faster fashion. Furthermore, due to higher titers reached after the primary immunization course, protective levels are retained for a longer period of time. Vaccination with FENDrix induces more transient local symptoms, with pain at the injection site being the most frequently reported solicited local symptom. Other symptoms such as fatigue, gastrointestinal disorders and headaches were also frequently observed but resolved without sequelae. The higher risk of hepatitis B transmission in patients with end-stage renal disease and the often immunocompromised status of these patients afford a tailored vaccination strategy that, up to now, has consisted of injecting double doses of ordinary hepatitis B vaccines. With the introduction of FENDrix there now exists an efficient alternative with superior immunogenicity that is, despite comparatively higher reactogenicity, well tolerated.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aluminum Compounds; Chemistry, Pharmaceutical; Hepatitis B; Hepatitis B Vaccines; Humans; Immunization Programs; Immunization Schedule; Kidney Failure, Chronic; Lipid A; Phosphates; Risk Factors; Vaccines, Synthetic

As new vaccines are developed, novel adjuvants may play an important role in eliciting an effective immune response. We evaluated the safety and adjuvant properties of monophosphoryl lipid A (MPL in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM(197) protein conjugate vaccine (PCV9) combined with 10, 25, or 50 micro g of MPL with or without alum (AlPO(4)). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL were well-tolerated and a dose-dependent effect of MPL on specific cellular responses was observed. The 10 micro g MPL dose significantly enhanced CRM(197)-specific T-cell proliferation (P=0.02) and interferon-gamma (INF-gamma) production (P=0.009) compared to responses of controls who received PCV9 with AlPO(4). In contrast, CRM(197)-specific T-cell proliferation and interferon-gamma production of the 50 micro g MPL/AlPO(4) group were decreased when compared to controls although these differences did not reach statistical significance. IL-5 and IL-13 responses after immunization showed a similar pattern with increased production in the 10 micro g MPL group and decreased production in the 50 micro g MPL/AlPO(4) group compared to controls. There were no differences in serum IgG antibody concentrations to the nine vaccine pneumococcal capsular polysaccharides and carrier protein between the MPL-containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL on T-helper cell type 1 (TH-1) responses to the carrier protein and also suggest an effect on T-helper cell type 2 (TH-2) responses.

Topics: Adjuvants, Immunologic; Aluminum Compounds; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Child, Preschool; Cytokines; Female; Humans; Immunity, Cellular; Immunoglobulin G; Infant; Lipid A; Lymphocyte Activation; Male; Phosphates; Polysaccharides, Bacterial; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer; Vaccines, Conjugate; Vaccines, Synthetic

A subunit vaccine, RBD-S, is under development to prevent severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV), which is classified by the US NIH as a category C pathogen. This vaccine is comprised of a recombinant receptor-binding domain (RBD) of the SARS-CoV spike (S) protein and formulated on alum, together with a synthetic glucopyranosyl lipid A. The vaccine would induce neutralizing antibodies without causing Th2-type immunopathology. Vaccine development is being led by the nonprofit product development partnership; Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development in collaboration with two academic partners (the New York Blood Center and University of Texas Medical Branch); an industrial partner (Immune Design Corporation); and Walter Reed Army Institute of Research. A roadmap for the product development of the RBD-S SARS vaccine is outlined with a goal to manufacture the vaccine for clinical testing within the next 5 years.

Topics: Adjuvants, Immunologic; Aluminum Compounds; Animals; Antibodies, Neutralizing; Antibodies, Viral; Antigens, Viral; Clinical Trials as Topic; Humans; Lipid A; Membrane Glycoproteins; Phosphates; Protein Structure, Tertiary; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Spike Glycoprotein, Coronavirus; Vaccines, Subunit; Vaccines, Synthetic; Viral Envelope Proteins; Viral Vaccines

The gram-negative, anaerobic bacterium Porphyromonas gingivalis, has been implicated in the etiology of adult periodontal disease. Among the potential virulence factors of this bacterium, the non-fimbrial adhesin hemagglutinin B (HagB) appears to be involved in the initial adherence of the bacteria to host tissue and the induction of anti-HagB antibody responses affords some protection from experimental alveolar bone loss. In the present study, we have investigated the ability of the quillaja saponin derivative GPI-0100 to act as an immunostimulant of responses to HagB following subcutaneous (s.c.) or intranasal (i.n.) immunization of mice. We have also compared the immunopotentiating ability of GPI-0100 with that of five other adjuvants. Evidence is provided that GPI-0100 was more effective than monophosphoryl lipid A and alum in inducing serum anti-HagB responses following s.c. immunization. A comparison of the responses induced following i.n. immunization with HagB and adjuvant revealed that the heat-labile toxin of Escherichia coli (LT) and the non-enzymatic mutant LT (E112K), followed by GPI-0100 potentiated higher serum and mucosal anti-HagB antibody responses, which in most cases were higher than those seen with the other adjuvants tested (i.e. monophosphoryl lipid A, alum and the B subunit of cholera toxin). Furthermore, a difference was seen in the nature of the serum IgG anti-HagB response based on the adjuvant used and route of immunization. These results demonstrate the effectiveness of GPI-0100 as both a systemic and mucosal adjuvant and support its potential use in the development of vaccines against periodontal, as well as other pathogens.

Topics: Adhesins, Bacterial; Adjuvants, Immunologic; Administration, Intranasal; Aluminum Compounds; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Cholera Toxin; Female; Hemagglutinins; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Injections, Subcutaneous; Lectins; Lipid A; Mice; Mice, Inbred BALB C; Mucous Membrane; Phosphates; Porphyromonas gingivalis; Quillaja; Recombinant Proteins; Saliva; Saponins; Vagina

Five adjuvants were tested for their effect on the immune response in guinea pigs to the hemagglutinin antigen of influenza virus strain B/Panama. Vaccines containing 924 micrograms of hemagglutinin antigen/ml were prepared at high and low doses of Freund's complete and incomplete adjuvants, Syntex adjuvant, RIBI's adjuvant, TiterMax adjuvant, and aluminum phosphate adjuvant. Responses to these vaccines were compared with those to a control vaccine containing influenza virus B/Panama hemagglutinin antigen and saline. On day 28, vaccines containing the following adjuvant doses had significantly higher titers than the titer for the control: Freund adjuvants at high and low doses, RIBI at high dose, TiterMax at high and low doses, and aluminum phosphate at high dose. On day 42, vaccines containing the following adjuvant doses had significantly higher titers than that for the control: Freund adjuvants at high and low doses, RIBI at high dose, TiterMax at high dose, and aluminum phosphate at high dose. Freund adjuvants at high and low doses, RIBI adjuvant at high dose, and aluminum phosphate at high dose caused significantly greater swelling at the inoculation site than did the control vaccine. TiterMax adjuvant at high and low doses, and aluminum phosphate at low dose caused minor swelling at the inoculation site, but it was not significantly different from the swelling caused by the control vaccine. Syntex adjuvant at high and low doses, RIBI at low dose, and control (saline/antigen) at high and low doses caused no swelling after inoculation. Overall, the high dose of adjuvants caused greater tissue swelling than did the low dose of adjuvants.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Aluminum Compounds; Animals; Antibodies, Viral; Antigens, Viral; Cell Wall Skeleton; Cord Factors; Freund's Adjuvant; Guinea Pigs; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Influenza B virus; Lipid A; Male; Phosphates; Poloxalene; Polysorbates; Squalene; Viral Envelope Proteins; Viral Vaccines