Michel Cadoz

Wistar Institute, Filadelfia, Pennsylvania, United States

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Publications (8)64.02 Total impact

  • C. Meric · M. Cadoz
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    ABSTRACT: Development of a vaccine for prevention of congenital cytomegalovirus (CMV) disease is a priority. This study evaluated a "prime-boost" strategy by comparing the safety and immunogenicity of 3 doses of subunit CMV glycoprotein B (gB) vaccine plus MF59 (a squalene-in-water emulsion), 2 doses of a canarypox recombinant vaccine expressing CMVgB (ALVAC-CMVgB) followed by 2 doses of the subunit gB vaccine, 3 doses of both vaccines administered concomitantly, and placebo in 105 healthy, CMV-seronegative adults. Systemic adverse events were rare, but local reactions were common in all groups. After the first subunit vaccination, neutralizing antibody titers in the prime-boost group were comparable to those in subjects receiving 2 subunit vaccinations, indicating a priming effect of ALVAC-CMVgB. However, after the final dose, antibody and cell-mediated immune responses were not significantly different among the groups. All 3 vaccine regimens induced high-titer antibody and lymphoproliferative responses, but no benefit for priming or simultaneous vaccination was detected.
    The Journal of Infectious Diseases 04/2002; 185(5):686-90. DOI:10.1086/339003 · 6.00 Impact Factor
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    ABSTRACT: The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.
    The Journal of Infectious Diseases 05/2001; 183(8):1171-9. DOI:10.1086/319680 · 6.00 Impact Factor
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    ABSTRACT: To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.
    The Journal of Infectious Diseases 10/1999; 180(3):843-6. DOI:10.1086/314951 · 6.00 Impact Factor
  • M Cadoz · C Méric
    Archives de Pédiatrie 02/1999; 6 Suppl 3:655s-658s. · 0.41 Impact Factor
  • M. Cadoz · C. Méric
    Archives de Pédiatrie 01/1999; 6. DOI:10.1016/S0929-693X(99)80388-1 · 0.41 Impact Factor
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    ABSTRACT: ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds.
    Developments in biological standardization 02/1995; 84:165-70.
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    ABSTRACT: Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.
    The Lancet 07/1992; 339(8807):1429-32. DOI:10.1016/0140-6736(92)92027-D · 45.22 Impact Factor