Studies
of a prophylactic HIV-1 vaccine candidate based on modified
vaccinia virus Ankara (MVA) with and without DNA priming:
effects of dosage and route on safety and immunogenicity.
Peters
BS, Jaoko W, Vardas E, Panayotakopoulos G, Fast P, Schmidt
C, Gilmour J, Bogoshi M, Omosa-Manyonyi G, Dally L, Klavinskis
L, Farah B, Tarragona T, Bart PA, Robinson A, Pieterse C,
Stevens W, Thomas R, Barin B, McMichael AJ, McIntyre JA, Pantaleo
G, Hanke T, Bwayo J. Kings College London, UK. Barry.Peters@kcl.ac.uk
BACKGROUND:
Two parallel studies evaluated safety and
immunogenicity of a prophylactic HIV-1 vaccine in 192 HIV-seronegative,
low-risk volunteers. Modified vaccinia virus Ankara (MVA)
and plasmid DNA (pTHr) expressed HIV-1 clade A gag p24 and
p17 fused to a string of 25 overlapping CD8+ T cell epitopes
(HIVA). METHODS: These studies compared intramuscular, subcutaneous,
and intradermal MVA at dosage levels ranging from 5x10(6)-2.5x10(8)
pfu. In Study IAVI-010, DNA vaccine was given as a prime at
months 0 and 1, followed by MVA as a boost at months 5 and
8. In Study IAVI-011, MVA alone was given at months 0 and
2. Regular safety monitoring was performed. Immunogenicity
was measured by the interferon (IFN)-gamma ELISPOT assay on
peripheral blood mononuclear cells (PBMC). RESULTS: No serious
adverse events were attributed to either vaccine; most adverse
events were mild or moderate, although MVA resulted in some
severe local reactions. Five vaccine recipients had at least
one positive IFN-gamma ELISPOT response, but none were sustained.
CONCLUSION: This HIV-1 vaccine candidate was in general safe
and well-tolerated. Local reactions were common, but tolerable.
Detectable immune responses were infrequent.
PMID: 17250931 [PubMed - indexed for MEDLINE]
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Luscher MA, Choy G, Njagi E, Bwayo JJ, Anzala AO, Ndinya-Achola
JO, Ball TB, Wade JA, Plummer FA, Barber BH, MacDonald KS.
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Department of Immunology, University of Toronto, The Toronto
Hospital, Canada.
In an effort to identify an immunological basis for natural
resistance to HIV-1 infection, we have examined serum antibody
responses to HLA class I antigens in female prostitutes of
the Nairobi Sex Workers Study. Anti-HLA antibodies are known
to block HIV infectivity in vitro and can be protective against
SIV challenge in macaques immunized with purified class I
HLA. Thus, it was postulated that broadly cross-reactive alloantibodies
recognizing common HLA alleles in the client population might
contribute to the prevention of heterosexual transmission
of HIV. In fact, 12% of the women were found to have serum
IgG antibodies against class I alloantigens. However, this
alloantibody did not correlate with the HIV status of the
women and was found in a similar proportion of HIV-positive
and HIV-resistant women. The observed levels of alloantibody
did not increase with HIV infection in susceptible individuals,
suggesting that potential antigenic mimicry between HIV and
host HLA class I antigens does not significantly increase
levels of anti-class I antibodies. The lack of correlation
between serum anti-allo-class I HLA antibodies and the risk
of sexual transmission indicates that this humoral immune
response is unlikely to be the natural mechanism behind the
HIV-resistance phenotype of persistently HIV-seronegative
women. This result, however, does not preclude the further
investigation of alloimmunization as an artificial HIV immunization
strategy.
PMID: 9462920 [PubMed - indexed for MEDLINE]
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