Evaluation in mice of the immunogenicity and protective efficacy of a tetravalent subunit vaccine candidate against dengue virus

A dengue vaccine must induce protective immunity against the four serotypes of the virus. Our group has developed chimeric proteins consisting of the protein P64k from Neisseria meningitidis and the domain III from the four viral envelope proteins. In this study, the immunogenicity of a tetravalent vaccine formulation using aluminum hydroxide as adjuvant was evaluated in mice. After three doses, neutralizing antibody titers were detected against the four viral serotypes, the lowest seroconversion rate being against dengue virus serotype 4. One month after the last dose, immunized animals were challenged with infective virus, and partial but statistically significant protection was found to have been achieved. Based on these results, further studies in mice and non‐human primates using this tetravalent formulation in a prime‐boost strategy with attenuated viruses are strongly recommended.

[1]  P. Chong,et al.  Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III. , 2013, Microbes and infection.

[2]  Chin-Cheng Huang,et al.  A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates , 2013, Archives of Virology.

[3]  M. Guzmán,et al.  A vaccine formulation consisting of nucleocapsid-like particles from Dengue-2 and the fusion protein P64k-domain III from Dengue-1 induces a protective immune response against the homologous serotypes in mice. , 2012, Acta tropica.

[4]  P. Chong,et al.  Dengue-1 Envelope Protein Domain III along with PELC and CpG Oligodeoxynucleotides Synergistically Enhances Immune Responses , 2012, PLoS neglected tropical diseases.

[5]  C. Huang,et al.  Recombinant Dengue Type 2 Viruses with Altered E Protein Domain III Epitopes Are Efficiently Neutralized by Human Immune Sera , 2012, Journal of Virology.

[6]  P. Chong,et al.  A Novel Single-Dose Dengue Subunit Vaccine Induces Memory Immune Responses , 2011, PloS one.

[7]  M. Guzmán,et al.  Nucleocapsid-like particles of dengue-2 virus enhance the immune response against a recombinant protein of dengue-4 virus , 2010, Archives of Virology.

[8]  M. Guzmán,et al.  Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use. , 2010, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[9]  Steven A. Ogata,et al.  Development of a recombinant tetravalent dengue virus vaccine: immunogenicity and efficacy studies in mice and monkeys. , 2010, Vaccine.

[10]  G. Chinea,et al.  A novel fusion protein domain III-capsid from dengue-2, in a highly aggregated form, induces a functional immune response and protection in mice. , 2009, Virology.

[11]  Bjoern Peters,et al.  A Protective Role for Dengue Virus-Specific CD8+ T Cells 1 , 2009, The Journal of Immunology.

[12]  M. Guzmán,et al.  Dengue‐4 envelope domain III fused twice within the meningococcal P64k protein carrier induces partial protection in mice , 2009, Biotechnology and applied biochemistry.

[13]  L. Lazo,et al.  The cellular immune response plays an important role in protecting against dengue virus in the mouse encephalitis model. , 2009, Viral immunology.

[14]  A. Yueh,et al.  A novel dengue vaccine candidate that induces cross-neutralizing antibodies and memory immunity. , 2009, Microbes and infection.

[15]  M. Guzmán,et al.  Immunogenicity and protective efficacy of a recombinant fusion protein containing the domain III of the dengue 1 envelope protein in non-human primates. , 2008, Antiviral research.

[16]  S. Halstead.  Pathogenesis: Risk Factors Prior to Infection , 2008 .

[17]  P. Desprès,et al.  Pediatric Measles Vaccine Expressing a Dengue Antigen Induces Durable Serotype-specific Neutralizing Antibodies to Dengue Virus , 2007, PLoS neglected tropical diseases.

[18]  G. Chinea,et al.  Amino acid changes in the recombinant Dengue 3 Envelope domain III determine its antigenicity and immunogenicity in mice. , 2006, Virus research.

[19]  L. E. Fernández,et al.  The enlargement of the hormone immune deprivation concept to the blocking of TGFα-autocrine loop: EGFR signaling inhibition , 2006, Cancer Immunology, Immunotherapy.

[20]  M. Guzmán,et al.  A recombinant fusion protein containing the domain III of the dengue-2 envelope protein is immunogenic and protective in nonhuman primates. , 2006, Vaccine.

[21]  S. Halstead,et al.  Dengue Virus Type 3, Cuba, 2000–2002 , 2005, Emerging infectious diseases.

[22]  M. Guzmán,et al.  A fragment of the envelope protein from dengue‐1 virus, fused in two different sites of the meningococcal P64k protein carrier, induces a functional immune response in mice , 2004, Biotechnology and applied biochemistry.

[23]  M. Guzmán,et al.  The fusion site of envelope fragments from each serotype of Dengue virus in the P64k protein, influence some parameters of the resulting chimeric constructs. , 2003, Biochemical and biophysical research communications.

[24]  R. Ahmed,et al.  Prolonged presence of effector‐memory CD8 T cells in the central nervous system after dengue virus encephalitis , 2003, International immunology.

[25]  R. Salas,et al.  Diversity and evolution of the envelope gene of dengue virus type 1. , 2002, Virology.

[26]  D. Vaughn,et al.  Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region. , 2001, The American journal of tropical medicine and hygiene.

[27]  G. Guillén,et al.  Safety and preliminary immunogenicity of the recombinant outer membrane protein P64k of Neisseria meningitidis in human volunteers , 2001, Biotechnology and applied biochemistry.

[28]  G. Murphy,et al.  Short report: Antibody responses of mice immunized with a tetravalent dengue recombinant protein subunit vaccine. , 2001, The American journal of tropical medicine and hygiene.

[29]  J. H. Strauss,et al.  Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response , 2000, Journal of Virology.

[30]  Viña,et al.  P64k Meningococcal Protein as Immunological Carrier for Weak Immunogens , 2000, Scandinavian journal of immunology.

[31]  R. Marks,et al.  Demonstration of binding of dengue virus envelope protein to target cells , 1996, Journal of virology.

[32]  S. Halstead,et al.  Simplified plaque reduction neutralization assay for dengue viruses by semimicro methods in BHK-21 cells: comparison of the BHK suspension test with standard plaque reduction neutralization , 1985, Journal of clinical microbiology.

[33]  J. Casals,et al.  Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. , 1958, The American journal of tropical medicine and hygiene.

[34]  G. Chinea,et al.  A dengue-2 Envelope fragment inserted within the structure of the P64k meningococcal protein carrier enables a functional immune response against the virus in mice. , 2004, Journal of virological methods.