Rotavirus vaccines hold promise to decrease the burden of severe diarrhea in the poorest countries, where 85% of deaths due to rotavirus occur. However, the potency of live oral vaccines is lower in these challenging settings than in middle- and upper-income countries. Many hypotheses have been suggested to explain these differences that could provide clues to improve the ultimate success of these novel vaccines. Although introduction today of even moderately effective vaccines will decrease the morbidity and mortality associated with rotavirus in low-income settings, research is urgently needed to understand why these differences in efficacy occur and what could be done to improve vaccine performance to maximize the life-saving benefits of vaccination.
Background: Live oral rotavirus vaccines have been less immunogenic and efficacious among children in poor developing countries compared with middle income and industrialized countries for reasons that are not yet completely understood. We assessed whether the neutralizing activity of breast milk could lower the titer of vaccine virus and explain this difference in vitro. Methods: Breast milk samples were collected from mothers who were breast-feeding infants 4 to 29 weeks of age (ie, vaccine eligible age) in India (N = 40), Vietnam (N = 77), South Korea (N = 34), and the United States (N = 51). We examined breast milk for rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains-RV1, RV5 G1, and 116E using enzyme immunoassays. The inhibitory effect of breast milk on RV1 was further examined by a plaque reduction assay. FINDINGS:: Breast milk from Indian women had the highest IgA and neutralizing titers against all 3 vaccine strains, while lower but comparable median IgA and neutralizing titers were detected in breast milk from Korean and Vietnamese women, and the lowest titers were seen in American women. Neutralizing activity was greatest against the 2 vaccine strains of human origin, RV1 and 116E. This neutralizing activity in one half of the breast milk specimens from Indian women could reduce the effective titer of RV1 by ∼2 logs, of 116E by 1.5 logs, and RV5 G1 strain by ∼1 log more than that of breast milk from American women. INTERPRETATION:: The lower immunogenicity and efficacy of rotavirus vaccines in poor developing countries could be explained, in part, by higher titers of IgA and neutralizing activity in breast milk consumed by their infants at the time of immunization that could effectively reduce the potency of the vaccine. Strategies to overcome this negative effect, such as delaying breast-feeding at the time of immunization, should be evaluated.
Background:
Diarrheal disease is a major cause of morbidity and mortality in humans and animals, including non human primates. While the diagnostics for gastrointestinal bacterial and parasitic pathogens and their etiological role in disease are well established, little is known about the epidemiology, prevalence and role of viral agents in diarrheal illness among monkeys.
Methods:
We collected fecal specimens from monkeys with diarrhea that were housed in two primate colonies, the Institute of Laboratory Animal Sciences, Beijing, China and the Yerkes National Primate Research Center, Georgia, USA. We screened these fecal specimens for rotaviruses and enteric adenoviruses 40/41 by using commercial EIA kits (Rotaclone and Adenoclone), enteroviruses by RT-PCR and Southern blot hybridization, and picobirnaviruses by polyacrylamide gel electrophoresis and silver staining. Some of the specimens were examined by EM for coronaviruses and noroviruses.
Results:
Of the 92 specimens from China, we found 63 (68%) positive for viruses, including enteroviruses (52%), enteric adenoviruses (21%), rotaviruses (20%), and picobirnaviruses (2%). Coronaviruses were detected in some specimens. Mixed infection of two or more viral agents was seen in 23 (25%) specimens. In the US collection, we detected enteroviruses and enteric adenoviruses in 76% (45/59) and 14% (7/50) of the specimens, respectively. Electron microscopy showed norovirus-like particles in some specimens from both colonies.
Conclusion:
Our findings indicate endemic infections with enteric viruses in monkeys of both colonies. The availability of new simian rotaviruses, enteric adenoviruses, enteroviruses, and coronaviruses and the discovery of noroviruses and picobirnaviruses may allow us to develop better diagnostics for these agents and determine which of these agents are clearly associated with gastroenteritis in monkeys.