Table of Contents

Volume 1, Issue 2

  March/April 2005

  Pages 45 - 90

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 Issue Catalogue (MARC XML)

REVIEW

Open Access Article

Role of Neutralizing Antibodies in Protective Immunity Against HIV

Indresh K. Srivastava, Jeffrey B. Ulmer and Susan W. Barnett
Pages 45 - 60
http://dx.doi.org/10.4161/hv.1.2.1764
Abstract | PDF

HIV continues to be a major health problem world wide, however the situation is particularly serious in Asian and Sub-Saharan countries. Therefore, development of an effective HIV vaccine could help to reduce the severity of the disease and prevent infection. Over the last two decades significant efforts have been made towards inducing potent humoral and cellular immune responses by vaccination, however antibodies and CTL responses alone are likely not sufficient for inducing sterilizing immunity or long-term control of viral replication. Therefore, it is generally believed that both humoral and cellular responses will be needed for an effective HIV vaccine. In support of humoral immunity, monoclonal antibodies that recognize critical neutralizing epitopes have shown to be effective at passive transfer experiments in conferring protection against challenge infection. However, antibodies to similar epitope specificities are difficult to induce by vaccination. Therefore, optimization of Env structure is needed for exposing appropriate neutralizing epitopes and masking non-neutralizing epitopes. Since the crystal structure of the core of Env glycoprotein has been solved, efforts are in progress to design novel Env immunogens that may induce effective neutralizing responses. Furthermore, there are HIV-1 strains that are resistant to neutralization by monoclonal antibodies, yet neutralized by pooled sera from HIV-1 patients. Therefore, efforts should be made to identify these novel epitopes and to design strategies to incorporate them in potential vaccines. To facilitate comparative evaluation of vaccine immunogens for their ability to induce cross clade neutralizing antibodies, efforts should be made to use standardized neutralization assays and standard virus panels. Once potent HIV Env structure have been identified, their effectiveness may be enhanced through the use of adjuvants, delivery systems and prime and boost strategies to improve the quality and magnitude of neutralizing responses.




RESEARCH PAPERS

Open Access Article

Immunogenicity and Tolerability of Intradermal Administration of an HCV E1-Based Vaccine Candidate in Healthy Volunteers and Patients with Resolved or Ongoing Chronic HCV Infection

Geert Leroux-Roels, Arsène-Hélène Batens, Isabelle Desombere, Bart Van Den Steen, Christine Vander Stichele, Geert Maertens and Frank Hulstaert
Pages 61 - 65
http://dx.doi.org/10.4161/hv.1.2.1554
Abstract | PDF

The tolerability and immunogenicity of intradermal injections of a candidate HCV vaccine, based on the E1 protein of the hepatitis C virus (HCV), was examined in an exploratory study in healthy volunteers, in subjects with a history of resolved HCV infection, and in patients suffering from therapy-resistant chronic HCV. Sub-epidermal injection of three doses of 4 µg of non-adjuvanted E1 vaccine induced much weaker humoral and cellular immune responses in healthy subjects and chronic HCV patients than the intramuscular administration of 20 µg E1 formulated on alum. However, in three subjects who cleared HCV infection, intradermal administration of this low dose of E1 induced rapid and clear anamnestic responses. These data demonstrate that E1-specific immune responses can be induced in resolving HCV infections and that memory (B and T) cells can be restimulated with suboptimal doses of E1 antigen.

Open Access Article

Delivering Pneumococcal Vaccine to a High Risk Population: The Navajo Experience

Andrea L. Benin, James P. Watt, Katherine L. O’Brien, Raymond Reid, Elizabeth R. Zell, Scott Katz, Connie Donaldson, Anne Schuchat, Mathuram Santosham and Cynthia G. Whitney
Pages 66 - 69
http://dx.doi.org/10.4161/hv.1.2.1562
Abstract | PDF

High rates of preventable diseases such as pneumococcal disease occur among the Navajo despite their universal health insurance through the Indian Health Service. The objective of this study was to determine the proportion of Navajo adults vaccinated with pneumococcal polysaccharide vaccine and to examine key features of vaccination programs of the Navajo Indian Health Service. For this cross-sectional study, medical charts of Navajo patients with vaccine indications were randomly selected and reviewed to determine who had been vaccinated as of January 1, 1999. Among 480 Navajo > 65 years old, 73% were vaccinated (95% confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine indications, 54% were vaccinated (95%CI: 45%-63%). Vaccination programs utilized extensive public health nursing, home visits, standing orders, and “express lane” clinics. In spite of excellent delivery systems and universal healthcare, the proportion of Navajo persons vaccinated was still below the goals for Healthy People 2010 of having 90% of persons >65 years old vaccinated and 60% of high-risk persons 18-64 years old vaccinated.

Open Access Article

Mechanism of Adsorption of Three Recombinant Streptococcus pneumoniae (Sp) Vaccine Antigens by an Aluminum Adjuvant

Philip M. Levesque and Uditha de Alwis
Pages 70 - 73
http://dx.doi.org/10.4161/hv.1.2.1592
Abstract | PDF

The adsorption of three Streptococcus pneumoniae (Sp) vaccine antigens by aluminum-containing adjuvants was studied. The antigens showed high binding affinity isotherms with aluminum hydroxide adjuvant described by the Langmuir equation but virtually no binding to aluminum phosphate adjuvant. The effects of ionic strength and ethylene glycol were evaluated to determine whether electrostatic or hydrophobic interactions were responsible for the observed binding to aluminum hydroxide, but no significant change in the adsorptive capacity was observed at either high ionic strength nor high concentrations of ethylene glycol for any of the antigens. This indicates that neither electrostatic nor hydrophobic interactions appear to be responsible for the observed binding, which means that ligand exchange may be the primary mechanism for this interaction. Further studies to evaluate the ability to elute a Sp antigen from aluminum hydroxide using fibrinogen (adsorptive coefficient 2.2 mL/µg) as a competitive protein resulted in evidence that Sp antigen follows the trend that proteins with higher adsorptive coefficients are able to displace those with lower adsorptive coefficients. It was also noted that the Sp antigens and ?-lactalbumin (adsorptive coefficient 1.8 mL/µg) have similar adsorptive coefficients indicative of high affinity binding isotherms but do not contain phosphate, which has previously been used to explain ligand exchange for such proteins as ?-casein and hepatitis B surface antigen (HBsAg). Further investigations using ?-lactalbumin as a model protein may elucidate the binding interaction between the antigens in this study and aluminum adjuvants.

Open Access Article

Physician Knowledge and Perspectives Regarding Influenza and Influenza Vaccination

Samuel R. Dominguez and Robert S. Daum
Pages 74 - 79
http://dx.doi.org/10.4161/hv.1.2.1604
Abstract | PDF

Background: Recent studies have demonstrated that healthy children younger than 24 months of age are at risk for influenza-associated hospitalization and influenza related complications. In light of this, the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention changed their recommendation for influenza vaccination for the 2004-05 season to include universal vaccination for all healthy children 6-23 months of age.

Methods: A self-administered survey was distributed to a random sampling of family practitioners and pediatricians in Chicago, IL. Questions were asked regarding demographics, current use of influenza vaccines, and knowledge regarding influenza vaccines and influenza infection in children. Answers were scored as correct based on published literature and AAP/ACIP recommendations.

Results: During the 2002-03 influenza season, physician-directed recommendation for influenza vaccination and physician perceived use for both healthy children and children with a high-risk medical condition were both low. The majority of physicians were not aware of the severity of influenza infection in young children, could not correctly identify all contraindications to receiving vaccination, did not know which children require two vaccinations, and were not aware of the complications of influenza in children.

Conclusions: To achieve the goal of universal influenza vaccination coverage for healthy children 6-23 months of age, physicians will need a greater understanding of the severity of influenza illness in this age group coupled with an increased knowledge of indications for vaccine administration.

Open Access Article

Characterisation of the Protein Content of a Meningococcal Outer Membrane Vesicle Vaccine by Polyacrylamide Gel Electrophoresis and Mass Spectrometry

Caroline Vipond, Jun X. Wheeler, Christopher Jones, Ian M. Feavers and Janet Suker
Pages 80 - 84
http://dx.doi.org/10.4161/hv.1.2.1651
Abstract | PDF

The development and evaluation of outer membrane vesicles as vaccines against meningococcal disease has been carried out for more than two decades. Although such vaccines have limitations and are not widely licensed, they continue to be used to disrupt clonal outbreaks caused by group B meningococci and a wealth of information is now available from large-scale clinical studies. One dimensional polyacrylamide gel electrophoresis and semi-quantitative measurement of the major proteins is one method used to evaluate and control these products. However, it is often difficult to determine exactly which bands on a one dimensional gel correspond to the key antigens whose presence must be demonstrated for control and lot release. We have therefore carried out mass spectrometric analyses of outer membrane vesicle vaccine samples to definitively identify the bands containing seven key antigens: Omp85, FetA, PorA, PorB, RmpM, OpcA and NspA. An additional 33 proteins present in the vaccine were also identified and this information will be useful both for future quality control and for the interpretation of data from vaccine trials.

Open Access Article

A Non-Living Nasal Influenza Vaccine Can Induce Major Humoral and Cellular Immune Responses in Humans without the Need for Adjuvants

Helvi Holm Samdal, Hilde Bakke, Fredrik Oftung, Johan Holst, Inger Lise Haugenb, Gro Ellen Korsvold, Anne-Cathrine Kristoffersen, Grethe Krogh, Karin Nord, Rino Rappuoli, Aud Katrine Herland Berstad and Bjørn Haneberg
Pages 85 - 90
http://dx.doi.org/10.4161/hv.1.2.1718
Abstract | PDF

Twenty-eight healthy adult volunteers were immunized intranasally with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1), either in saline or mixed with formaldehyde-inactivated Bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with mucoadhesive properties. After four doses, all groups of vaccinees developed significant IgG- and IgA-antibody responses, measured by ELISA, in respectively serum and nasal secretions. None of the volunteers had demonstrable hemagglutination inhibition (HAI) antibodies in serum before being immunized, whereas more than 80% of them reached HAI titers ? 40, considered protective, after immunizations. In addition, cellular immune responses, measured as significant increases in CD4+ T-cell proliferation and granzyme B-producing cytotoxic T-cells, were detected against the vaccine strain as well as against heterologous virus strains (H3N2). However, no additive effect on these responses could be demonstrated with use of B. pertussis or the thixotropic substance in the present vaccines. It appeared, actually, that the mucoadhesive vehicle containing the thixotropic substance was less efficient than were the two other formulations. An influenza vaccine made as a simple particulate formulation of inactivated virus, and given repeatedly onto the nasal mucosa, may thus be an attractive alternative to currently available vaccines.