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. 2010 Oct;16(10):1117-9.
doi: 10.1038/nm.2233. Epub 2010 Oct 3.

Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques

Cherie T Ng  1 , J Pablo Jaworski, Pushpa Jayaraman, William F Sutton, Patrick Delio, LaRene Kuller, David Anderson, Gary Landucci, Barbra A Richardson, Dennis R Burton, Donald N Forthal, Nancy L Haigwood
Affiliations

Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques

Cherie T Ng et al. Nat Med. 2010 Oct.

Abstract

Maternal HIV-1-specific antibodies are efficiently transferred to newborns, but their role in disease control is unknown. We administered neutralizing IgG, including the human neutralizing monoclonal IgG1b12, at levels insufficient to block infection, to six newborn macaques before oral challenge with simian-HIV strain SF162P3 (SHIV(SF162P3)). All of the macaques rapidly developed neutralizing antibodies and had significantly reduced plasma viremia for six months. These studies support the use of neutralizing antibodies in enhancing B cell responses and viral control in perinatal settings.

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Figures

Fig. 1
Fig. 1. Matched-IgG, but not Mismatched-IgG, affects plasma viral load in SHIVSF162P3-infected infant macaques
Neutralizing activity of Matched IgG, with IgG1-b12 (■) and without IgG1-b12 (□), and Mismatched IgG (●) against: the challenge virus SHIVSF162P3 (a) and heterologous virus SHIV89.6P (b). Vertical line at 2 × 103 denotes the estimated in vivo passive IgG concentration of 2 mg ml−1. (c) Mean PBMC proviral loads during the 24 weeks after initiation of infection as quantified by real-time PCR. (d) Mean plasma viral loads as quantified by real-time PCR during the 24 weeks after initiation of infection. (e) Differences in AUC comparing Normal-IgG, Mismatched-IgG, and Matched-IgG for the entire 24 weeks. (f) Differences in AUC calculations for post-acute viremia between all treatment groups (weeks 8–24). Horizontal bar indicates the median value for the group. P values are indicated.
Fig. 2
Fig. 2. Matched-IgG, but not Mismatched-IgG, improves humoral responses to 24 weeks post-infection
(a) Left panel, mean HIV-1SF162 gp120-specific IgG concentration (±SD) as determined by kinetic ELISA for animals treated with Normal IgG, Matched IgG, and Mismatched IgG; right panel, analysis of the longitudinal effect of the SHIVIG pre-treatments on Env-specific IgG development (weeks 8–24) using AUC analysis (Mann-Whitney U test). (b) Left panel, neutralizing activity in the plasma of each group was evaluated against SHIVSF162P3 clone MC17, reported as the mean titers (±SD) for each group. ID50 is the plasma dilution necessary to inhibit infection by 50%; right panel, area under the curve from 8 wpi to 24 wpi, and the Matched-IgG group had significantly higher titers than the controls (AUC, Mann-Whitney U test) while the Mismatched-IgG group did not. (c) Mean ADCVI levels (±SD) were evaluated to examine sources of virus inhibition other than neutralization. (d) At 24 weeks post-infection, CD4 counts within the Matched group remained above 250 cells µl−1 blood (dotted line) while the Mismatched group had > 50% of infants at or below this level. * denotes P-value < 0.01.
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