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Review
. 2018 Jan;13(1):97-118.
doi: 10.2217/fmb-2017-0128. Epub 2017 Dec 8.

Causes of impaired oral vaccine efficacy in developing countries

Edward Pk Parker  1 , Sasirekha Ramani  2 , Benjamin A Lopman  3 , James A Church  4 , Miren Iturriza-Gómara  5 , Andrew J Prendergast  4 , Nicholas C Grassly  1
Affiliations
Review

Causes of impaired oral vaccine efficacy in developing countries

Edward Pk Parker et al. Future Microbiol. 2018 Jan.

Abstract

Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms.

Keywords: cholera; enteropathy; histo blood group antigens; immunogenicity; malnutrition; microbiota; oral vaccines; poliovirus; rotavirus.

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Conflict of interest statement

Financial & competing interests disclosure

EPK Parker has received funding from the UK Medical Research Council. M Iturriza-Gómara has received research grant support form GlaxoSmithKline and Sanofi Pasteur MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Impaired immunogenicity of oral poliovirus vaccine in India.
Seroconversion rates for India are obtained from a report by John [194], which combines results from several trials of trivalent OPV performed in Vellore between 1969 and 1976. Immunogenicity data from the USA are obtained from a study by McBean et al. [195] in which three doses of trivalent OPV were administered to infants in Maryland at 2, 4 and 18 months of age. Seroprevalence estimates at 18 and 20 months of age are interpreted here as seroconversion. OPV: Oral poliovirus vaccine; PV1: Type 1 poliovirus; PV2: Type 2 poliovirus; PV3: Type 3 poliovirus.
<b>Figure 2.</b>
Figure 2.. Oral vaccine failure: a timeline of contributing factors.
EED: Environmental enteric dysfunction; HBGA: Histo blood group antigen; HMO: Human milk oligosaccharide.
<b>Figure 3.</b>
Figure 3.. Potential mechanisms underlying variation in oral vaccine efficacy.
Upon arrival at the gastrointestinal epithelium, multiple factors may impact the ability of an oral vaccine to replicate and/or cause a protective immune response. Breast milk IgA may neutralize the vaccine, as may infant IgA induced by prior exposure to the infection being targeted. HBGAs act as binding sites for many enteric infections. Their precise structure as well as their presence in mucosal secretions are genetically determined and vary among individuals. The presence of enteric pathogens at the time of immunization may activate innate immune pathways that inhibit the immunogenicity of oral vaccines. Repeated pathogen exposure may also give rise to enteropathy – a subclinical condition associated with increased gut permeability and the induction of a pro-inflammatory state that may inhibit oral vaccine immunogenicity. The bacterial microbiota is crucial both to the development of the intestinal immune system and the replication of enteric viruses. Perturbations of the microbiota (or dysbiosis) may therefore have an inhibitory effect on oral vaccines. Pathogen exposure, enteropathy and microbiota dysbiosis may also alter the adaptive response to oral vaccines; for example, by inducing regulatory T cells that promote a state of mucosal tolerance. Finally, transplacental IgG in infant serum has been shown to interfere with both oral and parenteral vaccines. HBGA: Histo blood group antigen.
<b>Figure 4.</b>
Figure 4.. Summary of evidence regarding mechanisms of oral vaccine failure.
See this image and copyright information in PMC

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