Skip to main content
Article thumbnail
Location of Repository

Dual Neonate Vaccine Platform against HIV-1 and M. tuberculosis

By Richard Hopkins, Anne Bridgeman, Joan Joseph, Sarah C. Gilbert, Helen McShane and Tomáš Hanke


Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the world's most devastating diseases. The first vaccine the majority of infants born in Africa receive is Mycobacterium bovis bacillus Calmette-Guérin (BCG) as a prevention against TB. BCG protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary TB and enhancing boost delivered by recombinant modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of M. tuberculosis is currently in phase IIb evaluation in African neonates. If the newborn's mother is positive for human immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring HIV-1 through breastfeeding. We suggested that a vaccination consisting of recombinant BCG expressing HIV-1 immunogen administered at birth followed by a boost with rMVA sharing the same immunogen could serve as a strategy for prevention of mother-to-child transmission of HIV-1 and rMVA expressing an African HIV-1-derived immunogen HIVA is currently in phase I trials in African neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1 and TB consisting of BCG.HIVA administered at birth followed by a boost with MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed, in which the transgene transcription is driven by either modified H5 or short synthetic promoters, respectively, and tested for immunogenicity alone and in combination with BCG.HIVA222. mMVA.HIVA.85A was produced markerless and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c mice. A BCG.HIVA222–mMVA.HIVA.85A prime-boost regimen induced robust T cell responses to both HIV-1 and M. tuberculosis. Therefore, proof-of-principle for a dual anti-HIV-1/M. tuberculosis infant vaccine platform is established. Induction of immune responses against these pathogens soon after birth is highly desirable and may provide a basis for lifetime protection maintained by boosts later in life

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2009). A prime-boost immunisation regimen using recombinant BCG and Pr55(gag) virus-like particle vaccines based on HIV type 1 subtype C successfully elicits Gag-specific responses in baboons.
    2. (2009). AIDS epidemic update. WHO Report.
    3. (1988). An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes.
    4. (2007). Clinical experience with plasmid DNA- and modified vaccinia vaccine Ankara (MVA)-vectored HIV-1 clade A vaccine inducing T cells.
    5. (1997). Compact, synthetic, vaccinia virus early/late promoter for protein expression.
    6. (1999). Comparison of the construction of unmarked deletion mutations in Mycobacterium smegmatis, Mycobacterium bovis bacillus Calmette-Guerin, and Mycobacterium tuberculosis H37Rv by allelic exchange.
    7. (2008). Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants.
    8. (1992). Construction of solid matrixantibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen.
    9. (2007). Cowpox virus evades CTL recognition and inhibits the intracellular transport of MHC class I molecules.
    10. (2007). Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination.
    11. (1988). Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen.
    12. (2008). Dendritic cells are preferentially targeted among hematolymphocytes by Modified Vaccinia Virus Ankara and play a key role in the induction of virus-specific T cell responses in vivo.
    13. (2000). Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya.
    14. (2009). Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines.
    15. (2007). Design and pre-clinical evaluation of a universal HIV-1 vaccine.
    16. (2008). Design, construction, and characterization of a multigenic modified vaccinia Ankara candidate vaccine against human immunodeficiency virus type 1 subtype C/B9.
    17. (1996). Development of a replicationdeficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model.
    18. (2005). Disruption of MHC class II-restricted antigen presentation by vaccinia virus.
    19. (1994). Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature.
    20. (2009). Elucidating and minimizing the loss by recombinant vaccinia virus of human immunodeficiency virus gene expression resulting from spontaneous mutations and positive selection.
    21. (2004). Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa.
    22. (2003). Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Gue ´rin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara.
    23. (2001). Enhanced immunogenicity of CD4(+) t-cell responses and protective efficacy of a DNA-modified vaccinia virus Ankara prime-boost vaccination regimen for murine tuberculosis.
    24. (2007). Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/ Gag-Pol-Nef antigens of clade C.
    25. (2005). Hill A
    26. (1993). Immunization with recombinant BCG-SIV elicits SIV-specific cytotoxic T lymphocytes in rhesus monkeys.
    27. (2004). Immunoprophylaxis to prevent mother-to-child transmission of HIV-1.
    28. (2006). Inhibition of CD1d1-mediated antigen presentation by the vaccinia virus B1R and H5R molecules.
    29. Investigating the induction of vaccine-induced Th17 and regulatory T cells in healthy, Mycobacterium bovis BCG-immunized adults vaccinated with a new tuberculosis vaccine, MVA85A.
    30. (2010). Modified H5 promoter improves stability of insert genes while maintaining immunogenicity during extended passage of genetically engineered MVA vaccines.
    31. (2010). Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells.
    32. (2010). Molecular characterization of heterologous HIV-1gp120 gene expression disruption in mycobacterium bovis BCG host strain: a critical issue for engineering mycobacterial based-vaccine vectors.
    33. (2004). MVA as a vector for vaccines against HIV-1. Expert Rev Vaccines 3:
    34. (2009). MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques.
    35. (1991). New use of BCG for recombinant vaccines.
    36. (2009). Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis.
    37. (2010). Novel recombinant Mycobacterium bovis BCG, ovine atadenovirus, and modified vaccinia virus Ankara vaccines combine to induce robust human immunodeficiency virus-specific CD4 and CD8 T-cell responses in rhesus macaques.
    38. (2009). Ovine atadenovirus, a novel and highly immunogenic vector in prime-boost studies of a candidate HIV-1 vaccine.
    39. (2005). Primingboosting vaccination with recombinant Mycobacterium bovis bacillus CalmetteGuerin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.
    40. (1993). Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis.
    41. (2010). Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.
    42. (2005). Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence.
    43. (2004). Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans.
    44. (2009). Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses.
    45. (2009). Safety and Immunogenicity of a New TB Vaccine, MVA85A, in M. tuberculosis Infected Individuals. Am J Respir Crit Care Med.
    46. (2009). Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A.
    47. (2010). Safety and immunogenicity of novel recombinant BCG and modified vaccinia virus Ankara vaccines in neonate rhesus macaques.
    48. (2006). Safety, immunogenicity, and efficacy of prime-boost immunization with recombinant poxvirus FP9 and modified vaccinia virus Ankara encoding the full-length Plasmodium falciparum circumsporozoite protein.
    49. (2004). The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKTmediated cytotoxicity against multiple targets in vitro and in vivo.
    50. (2007). Vaccine platform for prevention of tuberculosis and mother-to-child transmission of human immunodeficiency virus type 1 through breastfeeding.
    51. (2007). Vaccine properties of a novel marker gene-free recombinant modified vaccinia Ankara expressing immunodominant CMV antigens pp65 and IE1.
    52. (2009). Vaccinia virus decreases major histocompatibility complex (MHC) class II antigen Dual Vaccine Platform against HIV-1
    53. (2009). Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.