Research Article: Effect of HIV-exposure and timing of anti-retroviral treatment on immunogenicity of trivalent live-attenuated polio vaccine in infants

Date Published: April 19, 2019

Publisher: Public Library of Science

Author(s): Shelina Moonsamy, Melinda Suchard, Shabir A. Madhi, Heather B Jaspan.

http://doi.org/10.1371/journal.pone.0215079

Abstract

The prevalence of HIV infection in South African pregnant women has been approximately 30% over the past decade; however, there has been a steady decline in mother-to-child transmission of HIV from 8% in 2008 to <2% in 2015. We evaluated the immunogenicity of live-attenuated trivalent oral polio vaccine (OPV) following the primary vaccination series (doses at birth, 6, 10 and 14 weeks of age) in HIV-exposed uninfected (HEU), HIV-infected infants initiated on early anti-retroviral treatment (HIV+/ART+), HIV-infected infants on deferred ART (HIV+/ART-) and HIV-unexposed infants (HU) as the referent group. Serum polio neutralization antibody titres were evaluated to serotype-1, serotype-2 and serotype-3 at 6, 10 and 18 weeks of age. Antibody titres ≥8 were considered seropositive and sero-protective. At 18 weeks of age, following the complete primary series of four OPV doses, no differences in GMTs, percentage of infants with sero-protective titres and median fold change in antibody titre (18 weeks vs 6 weeks) were observed in HEU infants (n = 114) and HIV+/ART+ infants (n = 162) compared to HU infants (n = 104) for the three polio serotypes. However, comparing HIV+/ART- infants (n = 70) to HU infants at 18 weeks of age, we observed significantly lower GMTs for serotype-1 (p = 0.022), serotype-2 (p<0.001) and serotype-3 (p<0.001), significantly lower percentages of infants with sero-protective titres for the three serotypes (p<0.001), and significantly lower median fold change in antibody titre for serotype-1 (p = 0.048), serotype-2 (p = 0.003) and serotype-3 (p = 0.008). Delaying initiation of ART in HIV-infected infants was associated with an attenuated immune response to OPV following a four-dose primary series of vaccines, whereas immune responses to OPV in HIV-infected children initiated on ART early in infancy and HEU children were similar to HU infants.

Partial Text

Despite significant advances since the launch of the Global Polio Eradication Initiative in 1988, wild poliovirus and circulating vaccine-derived polioviruses remain a risk. The success of the Global Polio Eradication Initiative thus far is largely attributed to polio vaccination, with the key approach being to maintain vaccine coverage of more than 80% to optimise population immunity [1–3]. South Africa has a high prevalence of human immunodeficiency virus (HIV) in pregnant women, which has remained unchanged at around 30% for over a decade [4]. Although the percentage of infants born to HIV-infected women has remained fairly consistent since 2004, there has been a decline in mother-to-child transmission of HIV from 8% in 2008 to <2% in 2015 through effective perinatal HIV prevention programs, and therefore an increase in HIV-exposed uninfected (HEU) infants [4–6]. It has been demonstrated that HEU infants suffer increased morbidity and mortality than HIV-unexposed (HU) infants, although underlying reasons are unclear [7, 8]. Immunological aberrations, immune system impairment and reduced transfer of maternal antibodies have been reported in HEU infants compared to HU infants [7, 9, 10]. However, immune responses to vaccines in HEU infants has generally been similar to HU infants following routine immunisation schedules [9]. Demographic data as available and number of samples tested per group at each timepoint is shown in Table 1. To our knowledge, this is the first study in which the timing of ART initiation in HIV-infected infants on neutralising antibody immune responses to trivalent OPV was systematically evaluated. Trivalent OPV, containing all three serotypes, has since been replaced in April 2016 with bivalent OPV, containing serotype-1 and serotype-3, in a globally co-ordinated switch following the declaration of serotype-2 eradication in September 2015 [38, 39].   Source: http://doi.org/10.1371/journal.pone.0215079

 

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