Innate Immune Factors in Mothers' Breast Milk and Their Lack of Association With Rotavirus Vaccine Immunogenicity in Nicaraguan Infants

Becker‐Dreps, Sylvia; Choi, Wan Suk; Stamper, Lisa; Vílchez, Samuel; Velásquez, Daniel E.; Moon, Seol Ju; Hudgens, Michael G.; Jiang, Baoming; Permar, Sallie R.

doi:10.1093/jpids/piv076

Cited by 10 publications

(10 citation statements)

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“…Rotavirus-specific IgA and neutralizing antibody titers tend to be significantly higher in breast milk obtained from mothers in low-income countries (e.g., India and Bangladesh) compared with mothers from high-income countries (e.g., the USA and Sweden) and in the rotavirus high season compared with the low season [23,55,56]. Similarly, higher levels of lactoferrin and lactadherin have been observed in breast milk obtained from Indian and South-African women compared with North-American women [57], although these innate immune factors did not correlate with RotaTeq immunogenicity in a recent study in Nicaragua [58]. In the case of poliovirus, significantly higher IgA titers were documented in breast milk samples from unvaccinated women from Pakistan compared with vaccinated women from Japan or Sweden in the early 1990s [59], and it is likely that similar discrepancies between endemic and nonendemic settings persist today.…”

Section: Breastfeedingmentioning

confidence: 91%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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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. Enteric pathogens are a substantial threat to public health. This threat takes many forms, from the toxin-producing bacteria (e.g., Vibrio cholerae) and flagellated protozoa (e.g., Giardia lamblia) that colonize the mucosal surface of the small intestine to the enteroviruses that are capable of spreading via the bloodstream to the CNS, causing acute flaccid paralysis (e.g., poliovirus). Each year, enteric pathogens cause hundreds of millions of cases of diarrhea and approximately 800,000 deaths, the vast majority of which occur among children in low-income countries [1]. The most common causes of childhood diarrheal morbidity include rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli and Shigella [2].Vaccines against enteric pathogens are important tools for mitigating this disease burden. Oral vaccines offer several distinct benefits compared with parenteral vaccines. They can be produced in large quantities at relatively low cost, are easy to administer and have the capacity to induce local immunity in the intestinal mucosa, thereby protecting vaccinated individuals against subsequent infection and -by blocking onward transmission -enhancing herd immunity [3,4]. Currently licensed oral vaccines include live-attenuated poliovirus vaccines containing one, two or three serotypes, live-attenuated rotavirus vaccines (Rotarix R , RotaTeq R , Lanzhou lamb rotavirus vaccine [China only] and Rotavac R [India only]), live-attenuated cholera vaccine (CVD 103-HgR or Vaxchora TM ), inactivated cholera vaccines (Dukoral R and Shanchol R ) and live-attenuated typhoid vaccine (Ty21a). Other oral vaccines are in development, including those against Shigella, enterotoxigenic E. coli, Campylobacter and Clostridium difficile, as well as several novel rotavirus vaccine candidates (including the human neonatal vaccine RV3-BB [5] and an oral bovine pentavalent vaccine [6]).Yet oral vaccines have an Achilles' heel -their immunogenicity and efficacy is impaired in low-income countries that experience the greatest burden of enteric disease (Box 1). For example, Rotarix has a 1-year protective efficacy against severe rotavirus-associated gas...

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Section: Breastfeedingmentioning

confidence: 91%

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

et al. 2017

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“…Yet a study conducted in Nicaragua did not find an association between rotavirus-specific IgA titers in breast milk on the day of infant immunization and the immunogenicity of the pentavalent RV (22). Further, they did not find an association between the innate antiviral factors in breast milk, including lactoferrin, lactadherin, and tenascin-C, and RV responses (57).…”

Section: Observational Clinical Studies Of Maternal Immunity and Rotamentioning

confidence: 93%

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

Mwila

Chilengi

Simuyandi

et al. 2017

Clin Vaccine Immunol

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The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low-and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues. KEYWORDS immunization, low-and middle-income countries, maternal, rotavirus D espite the progress seen with the global introduction of rotavirus vaccines (RV), diarrhea is still a leading cause of death in children under the age of 5 years, and a substantial proportion of disease cases are still attributable to rotavirus infection. The latest estimates show that approximately 215,000 children die each year from rotavirusassociated diarrhea, and approximately 56% of these deaths are in sub-Saharan Africa (1). The World Health Organization (WHO) recommended the introduction of oral RV into national immunization programs (2), and many countries have heeded this call. As of September 2016, the WHO lists 86 countries as having included RV in their national immunization programs, and 6 more are in the course of doing so in 2016 (www.who.int/immunization/monitoring_surveillance/VaccineIntroStatus.pptx). Approximately 50% of the countries in Africa and Asia, over 80% of those in North America, South America, and Australia, and approximately 40% of those in Europe have introduced RV. Following RV introduction, there was a notable reduction in the number of deaths due to diarrhea (1). However, there is consistent evidence from clinical trials that RV have lower efficacies in low-and middle-income countries (LMIC): vaccine efficacies are 80 to 90% in high-income countries (HIC) and 40 to 60% in LMIC (3-8). Indeed, there is growing evidence from vaccine effectiveness studies emerging from the field that in real-life use, vaccine effectiveness is also consistently lower in LMIC (9-12).In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23] [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease. This review examines the correlations between maternal immune factors and RV responses and their potential effect on vaccine efficacy. NATURAL ROTAVIRUS...

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“…Tenascin-C (TNC) has also recently become the focus of research as another non-immunological breast milk component that has shown activity against the HIV virus through possible blocking of the HIV-1 envelope and might therefore contribute to breast milk viral neutralizing properties [ 16 ]. Work from Nicaragua failed to show any associations between innate immune factors LF, LA or TNC and seroconversion of infants to pentavalent rotavirus vaccine (RV5) [ 17 ]. This difference in results between Moon and colleagues [ 15 ] and Becker-Dreps and colleagues [ 17 ] shows the need to determine which are key factors in the various settings.…”

Section: Introductionmentioning

confidence: 99%

“…Work from Nicaragua failed to show any associations between innate immune factors LF, LA or TNC and seroconversion of infants to pentavalent rotavirus vaccine (RV5) [ 17 ]. This difference in results between Moon and colleagues [ 15 ] and Becker-Dreps and colleagues [ 17 ] shows the need to determine which are key factors in the various settings.…”

Section: Introductionmentioning

confidence: 99%

Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia

et al. 2017

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IntroductionRotavirus vaccines have been introduced into national immunization programmes to mitigate morbidity and mortality associated rotavirus diarrhoea. Lower vaccine effectiveness has however been noted in low-middle income countries, but little is known about the role of maternal components found in breast milk. This study assessed the effect of lactoferrin, lactadherin, and tenascin-c on rotavirus vaccine seroconversion.MethodsThis was a retrospective cohort study of 128 infants who had been fully immunized with Rotarix™. Serum samples were collected from the infant at baseline and one month after second rotavirus vaccine dose. Breast milk samples were collected from mothers at baseline. Standard ELISA was used to determine titres of rotavirus-specific immunologlobulin G and A in breast milk and serum as well as concentrations of lactoferrin, lactadherin, and tenascin-c. Poisson regression model with robust standard error was used to estimate the effect of breast milk components on seroconversion. The components were modelled on log base 2 so that the effect would be interpreted as a doubling of the concentration.ResultsIn a multivariable analysis adjusting for maternal age, maternal HIV status, seropositivity at baseline, sex, age of child at vaccination as well as breast milk IgA and IgG, we found evidence of independent effect of LA (Adjusted IRR = 0.95; 95% CI = 0.91–0.99; P = 0.019) on seroconversion while there was no evidence for TNC (Adjusted IRR = 1.00; 95% CI = 0.85–1.17; P = 0.967) and LF (Adjusted RR = 1.01; 95% CI = 0.96–1.05); P = 0.802). We explored the joint effects of the three components but we found no evidence (Adjusted RR = 0.95; 95% CI = 0.81; P = 0.535).ConclusionHigh breast milk concentrations of lactadherin might play a role in infant’s failure to seroconvert to rotavirus vaccines. Further research to understand this observed association is an important consideration.

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Innate Immune Factors in Mothers' Breast Milk and Their Lack of Association With Rotavirus Vaccine Immunogenicity in Nicaraguan Infants

Cited by 10 publications

References 14 publications

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia

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