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. 2009 Oct 1;200(7):1031-8.
doi: 10.1086/605648.

HIV-1 infection in Zambian children impairs the development and avidity maturation of measles virus-specific immunoglobulin G after vaccination and infection

Nitya Nair  1 , William J Moss, Susana Scott, Nanthalile Mugala, Zaza M Ndhlovu, Kareem Lilo, Judith J Ryon, Mwaka Monze, Thomas C Quinn, Simon Cousens, Felicity Cutts, Diane E Griffin
Affiliations

HIV-1 infection in Zambian children impairs the development and avidity maturation of measles virus-specific immunoglobulin G after vaccination and infection

Nitya Nair et al. J Infect Dis. .

Abstract

Background: Endemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects that HIV infection has on immune responses to measles and to measles vaccine can impact measles elimination efforts. Assays to measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) to all measles virus (MV) proteins, and the plaque reduction neutralization (PRN) assay, which measures antibody to the hemagglutinin and correlates with protection. Antibody avidity may affect neutralizing capacity.

Methods: HIV-infected and HIV-uninfected Zambian children were studied after measles vaccination (n=44) or MV infection (n=57). Laboratory or wild-type MV strains were used to infect Vero or Vero/signaling lymphocyte-activation molecule (SLAM) cells in PRN assays. IgG to MV was measured by EIA, and avidity was determined by ammonium thiocyanate dissociation.

Results: HIV infection impaired EIA IgG responses after vaccination and measles but not PRN responses measured using laboratory-adapted MV. Avidity was lower among HIV-infected children 3 months after vaccination and 1 and 3 months after measles. Neutralization of wild-type MV infection of Vero/SLAM cells correlated with IgG avidity.

Conclusion: Lower antibody quality and quantity in HIV-infected children after measles vaccination raise challenges for assuring the long-term protection of these children. Antibody quality in children receiving antiretroviral therapy requires assessment.

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Conflict of interest statement

Potential conflicts of interest: none reported.

Figures

Figure 1
Figure 1
Geometric mean titers (GMTs) of measles virus (MV)–specific neutralizing antibodies after vaccination and after natural infection in human immunodeficiency virus (HIV)–infected and HIV-uninfected children. Plaque reduction neutralization (PRN) after vaccination was measured using the Edmonston strain of MV to infect Vero cells [10] (A). PRN after natural MV infection was measured using the Chicago-1 strain of MV to infect Vero (B) or Vero/signaling lymphocyte-activation molecule (C) cells. White bars indicate HIV-uninfected children, checkered bars indicate HIV-infected children, error bars indicate interquartile ranges, and dashed lines indicate the generally accepted protective level of PRN antibody (120 mIU/mL).
Figure 2
Figure 2
Measles virus–specific immunoglobulin G antibody responses, determined by enzyme immunoassay after vaccination (A) and infection (B) in human immunodeficiency virus (HIV)–uninfected (white boxes) and HIV-infected (checkered boxes) children. Boxes indicate upper and lower quartiles, lines inside boxes indicate medians, and whisker bars indicate the 10th and 90th percentiles. P values were determined by the Wilcoxon signed-rank test or the Wilcoxon rank-sum test. OD405, optical density read at 405 nm.
Figure 3
Figure 3
Isotypes of measles virus–specific immunoglobulin G (IgG) responses after vaccination (A) and infection (B), as determined by enzyme immunoassay. OD655, optical density read at 655 nm.
Figure 4
Figure 4
Measles virus–specific immunoglobulin G (IgG) avidity maturation after vaccination (A) and infection (B) in human immunodeficiency virus (HIV)–uninfected (white boxes) and HIV-infected (checkered boxes) children. Boxes indicate upper and lower quartiles, lines inside boxes indicate median values, and whisker bars indicate 10th and 90th percentiles. P values were determined by the Wilcoxon-signed rank test or the Wilcoxon rank-sum test.
Figure 5
Figure 5
Linear regression analysis showing correlation between avidity index and plaque reduction neutralization for plasma samples from children with measles tested on Vero (A) and Vero/signaling lymphocyte-activation molecule (SLAM) (B) cells using Chicago-1 measles virus and on Vero/SLAM cells using a wild-type measles virus isolate from Zambia (C).
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