National Centers for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Pediatr Infect Dis J. 2010 Oct;29(10):919-23. doi: 10.1097/INF.0b013e3181e232ea.
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.
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.
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.
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.
活口服轮状病毒疫苗在贫穷的发展中国家儿童中的免疫原性和功效不如中低收入和工业化国家,其原因尚不完全清楚。我们评估了母乳的中和活性是否会降低疫苗病毒的效价,并在体外解释这种差异。
从印度(N=40)、越南(N=77)、韩国(N=34)和美国(N=51)正在母乳喂养 4 至 29 周龄婴儿(即疫苗接种年龄)的母亲中收集母乳样本。我们使用酶免疫测定法检测母乳中针对轮状病毒的特异性 IgA 和针对 3 种轮状病毒疫苗株(RV1、RV5 G1 和 116E)的中和活性。通过蚀斑减少测定法进一步研究了母乳对 RV1 的抑制作用。
印度妇女的母乳对所有 3 种疫苗株的 IgA 和中和滴度最高,而韩国和越南妇女的母乳中则检测到较低但相当的中位 IgA 和中和滴度,美国妇女的滴度最低。针对 2 种源自人类的疫苗株(RV1 和 116E)的中和活性最强。印度妇女一半的母乳样本中的这种中和活性可使 RV1 的有效滴度降低约 2 个对数,116E 的滴度降低 1.5 个对数,RV5 G1 株的滴度降低约 1 个对数,高于美国妇女的母乳。
贫穷发展中国家轮状病毒疫苗的免疫原性和功效较低,部分原因可能是其婴儿在免疫接种时摄入的母乳中 IgA 和中和活性较高,可有效降低疫苗的效力。应评估诸如延迟免疫接种时的母乳喂养等策略,以克服这种负面影响。