Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies - PubMed (original) (raw)

Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies

K J Stittelaar et al. J Virol. 2000 May.

Abstract

Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.

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Figures

FIG. 1

FIG. 1

Expression of MV F and H glycoproteins by MVA-FH. (A) Diagram of the genome of MVA-FH. del II, deletion II; del III, deletion III; PH5, modified H5 promoter; P7.5, 7.5 promoter. (B) Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methione-labeled proteins from CEF infected with MVA-FH and immunoprecipitated with measles polyclonal antibody. MW, molecular weights of marker proteins in thousands. The positions of MV H, F0, F1, and F2 proteins are indicated.

FIG. 2

FIG. 2

Development of VN antibody responses in plasma of macaques vaccinated at weeks 0 and 4 (indicated with arrows) with MVA-FH in the absence (group A) or in the presence (group B) of passively transferred MV-specific VN antibodies.

FIG. 3

FIG. 3

Development of MV glycoprotein-specific plasma IgG responses in macaques vaccinated at weeks 0 and 4 (indicated with arrows) with MVA-FH in the absence (A) or in the presence (B) of passively transferred MV-specific VN antibodies. The control macaques (C) were vaccinated with MVA-wt.

FIG. 4

FIG. 4

Development of MVA-specific plasma IgG responses. The first and second vaccinations are indicated with arrows.

FIG. 5

FIG. 5

Development of MV glycoprotein-specific plasma IgG responses in macaques vaccinated at weeks 0 and 4 with MV-Schwarz or rVV-FH in the absence (A and B, respectively) and presence (C and D, respectively) of MV-specific VN antibodies. p.i., passively immunized; ND, not done (due to unavailability of historical plasma).

FIG. 6

FIG. 6

MV-specific T-cell responses in PBMC bulk cultures of macaques 8 weeks after vaccination with MVA-FH in the absence (A) or presence (B) of passively transferred MV-specific VN antibodies or with MVA-wt (C). PBMC were stimulated once in vitro with autologous MV-infected mac.B-LCL cells and expanded in the presence of rhIL-2 alone or in the presence of both rhIL-2 and rhIL-4 (indicated with an asterisk). After 12 to 14 days, cells were harvested and treated with chymotrypsin to strip preexisting CD69 molecules from the membrane surface. Subsequently, cells were restimulated for 6 h with UV-inactivated autologous MV-infected mac.B-LCL cells, uninfected mac.B-LCL cells, or without mac.B-LCL cells (medium), and the membrane expression of CD3, CD8, and CD69 was determined. The percentages of CD69-positive cells in the CD3+ lymphocytes, as gated on the basis of an FSC/SSC plot, are shown for CD8+ (I) and CD8− (II) cells. ND, not done (because no cells could be expanded).

FIG. 7

FIG. 7

Number of MV-infected cells/106 LLC (open bars) or PBMC (black bars) at different times after intratracheal challenge with 103 TCID50s of MV-BIL. Macaques had been vaccinated with MVA-FH in the absence (A) or in the presence (B) of passively transferred MV-specific VN antibodies or with MVA-wt (group C). +, time point at which MV could be reisolated from PEC.

FIG. 8

FIG. 8

Development of MV glycoprotein-specific plasma IgG and VN antibody responses in macaques at different times after intratracheal challenge with 103 TCID50s of MV-BIL. Macaques had been vaccinated with MVA-FH in the absence (A) or in the presence (B) of passively transferred MV-specific VN antibodies or with MVA-wt (C).

FIG. 9

FIG. 9

Development of MV-N-specific plasma IgM responses in macaques at different times after intratracheal challenge with 103 TCID50s of MV-BIL. Macaques had been vaccinated with MVA-FH in the absence (A) or in the presence (B) of passively transferred MV-specific VN antibodies or with MVA-wt (C).

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