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. 2003 Jan;77(1):179-90.
doi: 10.1128/jvi.77.1.179-190.2003.

Immunization of newborn rhesus macaques with simian immunodeficiency virus (SIV) vaccines prolongs survival after oral challenge with virulent SIVmac251

Koen K A Van Rompay  1 , Jennifer L Greenier, Kelly Stefano Cole, Patricia Earl, Bernard Moss, Jonathan D Steckbeck, Bapi Pahar, Tracy Rourke, Ronald C Montelaro, Don R Canfield, Ross P Tarara, Christopher Miller, Michael B McChesney, Marta L Marthas
Affiliations

Immunization of newborn rhesus macaques with simian immunodeficiency virus (SIV) vaccines prolongs survival after oral challenge with virulent SIVmac251

Koen K A Van Rompay et al. J Virol. 2003 Jan.

Abstract

There is an urgent need for active immunization strategies that, if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (HIV) infection through breast-feeding. Better knowledge of the immunogenic properties of vaccine candidates in infants and of the effect of maternal antibodies on vaccine efficacy will aid in the development of such a neonatal HIV vaccine. Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model of pediatric HIV infection with which to address these questions. Groups of infant macaques were immunized at birth and 3 weeks of age with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol, and Env (MVA-SIVgpe) or live-attenuated SIVmac1A11. One MVA-SIVgpe-immunized group had maternally derived anti-SIV antibodies prior to immunization. Animals were challenged orally at 4 weeks of age with a genetically heterogeneous stock of virulent SIVmac251. Although all animals became infected, the immunized animals mounted better antiviral antibody responses, controlled virus levels more effectively, and had a longer disease-free survival than the unvaccinated infected monkeys. Maternal antibodies did not significantly reduce the efficacy of the MVA-SIVgpe vaccine. In conclusion, although the tested vaccines delayed the onset of AIDS, further studies are warranted to determine whether a vaccine that elicits stronger early immune responses at the time of virus exposure may be able to prevent viral infection or AIDS in infants.

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Figures

FIG. 1.
FIG. 1.
Comparison of survival for vaccinated and unvaccinated infant rhesus macaques. The survival of unvaccinated (dashed line) and vaccinated (solid lines) animals by age (weeks) is shown. The comparison of survival curves was performed by using the log-rank test. The median survival time for unvaccinated animals was 13 weeks of age. The survival curves for unvaccinated animals were statistically different from animals vaccinated with SIVmac1A11 (P < 0.0049 [•]) and all eight animals vaccinated with MVA-SIVgpe (P < 0.0093 [triangles]). There was no statistically significant difference in the survival curves among the different groups of vaccinated animals (MVA-SIVgpe immunized, median survival = 27 weeks [▿]; MVA-SIVgpe plus maternal SIV antibodies, median survival = 27.5 weeks [▾]; SIVmac1A11-immunized, all animals healthy at 28 weeks).
FIG. 2.
FIG. 2.
Virus levels in blood. Levels of SIV RNA in plasma (top panel) were measured by bDNA assay, whereas cell-associated virus levels (bottom panel) were measured by limiting dilution assay. Vaccine (V) was administered within 3 days after birth and 3 weeks later. All monkeys were challenged (C) orally with SIVmac251 at 4 weeks of age.
FIG. 3.
FIG. 3.
Measurements of quantitative and qualitative antibody responses in infant macaques orally inoculated with SIVmac251. Quantitative levels of SIV whole virus (A) and gag-specific (B) antibodies were determined in a standard ELISA. SIV Env-specific antibody endpoint titers (C), avidity (D), and conformational dependence (E) were determined in a ConA ELISA. All procedures are described in Materials and Methods.
FIG. 4.
FIG. 4.
Lymphocyte subsets in peripheral blood as measured by flow cytometric analyses. The percentages are expressed as fractions of the total number of lymphocytes.
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