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1.
Vaccine ; 27(43): 5998-6003, 2009 Oct 09.
Article in English | MEDLINE | ID: mdl-19665606

ABSTRACT

The standard serological methods present limitations for the measurement of immunity against H5N1 influenza strains. The hemagglutination inhibition (HI) assay lacks sensitivity and requires standardization, while the viral micro-neutralization (MN) assay needs handling of live virus. We produced pseudoparticles expressing hemagglutinin from clades 1 or 2 H5N1 in order to measure neutralizing antibodies in human sera after prime-boost vaccination with plain or MF59-adjuvanted H5N1 clade 1 subunit vaccines. Titers measured by pseudoparticle neutralization (PPN) assay significantly correlated with those measured by HI, single radial haemolysis or MN, with a PPN titer of 1:357 corresponding to an MN titer of 1:80. Notably, results from the PPN assay, confirm that MF59-H5N1 vaccine induces potent and long-lasting neutralizing antibody responses not only against the vaccine strain, but also against several heterologous clade 2 strains. Overall, the PPN assay represents a valid alternative to conventional serological methods for the evaluation of H5N1 vaccine immunogenicity.


Subject(s)
Antibodies, Viral/blood , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adult , Cross Reactions , Hemagglutination Inhibition Tests , Humans , Influenza, Human/immunology , Neutralization Tests
2.
Proc Natl Acad Sci U S A ; 106(10): 3877-82, 2009 Mar 10.
Article in English | MEDLINE | ID: mdl-19237568

ABSTRACT

Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4(+) T cells broadly reactive with drifted H5. The CD4(+) response was dominated by IL-2(+) IFN-gamma(-) IL-13(-) T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4(+) T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4(+) T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , Influenza A Virus, H5N1 Subtype/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Polysorbates/administration & dosage , Squalene/administration & dosage , Adjuvants, Immunologic/pharmacology , Adult , Antibody Formation/drug effects , CD4-Positive T-Lymphocytes/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Immunologic , Humans , Immunologic Memory/drug effects , Influenza A Virus, H5N1 Subtype/drug effects , Influenza Vaccines/pharmacology , Neutralization Tests , Phenotype , Polysorbates/pharmacology , Squalene/pharmacology , Th1 Cells/cytology , Th1 Cells/drug effects , Th1 Cells/immunology , Time Factors , Vaccination
3.
Vaccine ; 26(4): 552-61, 2008 Jan 24.
Article in English | MEDLINE | ID: mdl-18162266

ABSTRACT

Influenza is controlled by protective titres of neutralizing antibodies, induced with the help of CD4 T-cells, and by antiviral T-cell effector function. Adjuvants are essential for the efficient vaccination of a naïve population against avian influenza. We evaluated a range of adjuvants for their ability to enhance, in naïve mice, protective hemagglutination inhibition (HI) titres, which represent the generally accepted correlate of protection, virus-neutralizing titres and T-cell responses to a new generation influenza vaccine produced in cell culture. The selected adjuvants include alum, calcium phosphate (CAP), MF59, the delivery system poly-(lactide co-glycolide) (PLG) and the immune potentiator CpG. MF59 was clearly the most potent single adjuvant and induced significantly enhanced, long-lasting HI and neutralizing titres and T-cell responses in comparison to all alternatives. The combination of alum, MF59, CAP or PLG with CpG generally induced slightly more potent titres. The addition of CpG to MF59 also induced a more potent Th1 cellular immune response, represented by higher IgG2a titres and the induction of a strongly enhanced IFN-gamma response in splenocytes from immunized mice. These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains.


Subject(s)
Adjuvants, Immunologic , Influenza Vaccines/immunology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae/immunology , Squalene/immunology , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibody Specificity , Calcium Phosphates/immunology , Cell Line , Emulsions , Female , Immunoglobulin G/blood , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Influenza Vaccines/administration & dosage , Injections, Intramuscular , Interferon-gamma/biosynthesis , Lactic Acid/immunology , Mice , Mice, Inbred BALB C , Neutralization Tests , Polyglycolic Acid , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Polysorbates , Spleen/immunology , Th1 Cells/immunology , Th1 Cells/metabolism , Vaccines, Subunit/administration & dosage , Vaccines, Subunit/immunology
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