The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Infect Immun. 2010 May;78(5):1963-78. doi: 10.1128/IAI.01365-09. Epub 2010 Feb 16.
Pregnant women are infected by specific variants of Plasmodium falciparum that adhere and accumulate in the placenta. Using serological and molecular approaches, we assessed the global antigenic diversity of surface antigens expressed by placenta-binding isolates to better understand immunity to malaria in pregnancy and evolution of polymorphisms and to inform vaccine development. We found that placenta-binding isolates originating from all major regions where malaria occurs were commonly recognized by antibodies in different populations of pregnant women. There was substantial antigenic overlap and sharing of epitopes between isolates, including isolates from distant geographic locations, suggesting that there are limitations to antigenic diversity; however, differences between populations and isolates were also seen. Many women had cross-reactive antibodies and/or a broad repertoire of antibodies to different isolates. Studying VAR2CSA as the major antigen expressed by placenta-binding isolates, we identified antibody epitopes encoded by variable sequence blocks in the DBL3 domain. Analysis of global var2csa DBL3 sequences demonstrated that there was extensive sharing of variable blocks between Africa, Asia, Papua New Guinea, and Latin America, which likely contributes to the high level of antigenic overlap between different isolates. However, there was also evidence of geographic clustering of sequences and differences in VAR2CSA sequences between populations. The results indicate that there is limited antigenic diversity in placenta-binding isolates and may explain why immunity to malaria in pregnancy can be achieved after exposure during one pregnancy. Inclusion of a limited number of variants in a candidate vaccine may be sufficient for broad population coverage, but geographic considerations may also have to be included in vaccine design.
孕妇被特定的恶性疟原虫变体感染，这些变体附着并积累在胎盘上。我们采用血清学和分子方法，评估了与胎盘结合的寄生虫分离株所表达的表面抗原的全球抗原多样性，以更好地了解妊娠期间疟疾的免疫反应和多态性的演变，并为疫苗开发提供信息。我们发现，来自疟疾主要发生地区的胎盘结合分离株通常被不同孕妇群体的抗体识别。分离株之间存在大量的抗原重叠和表位共享，包括来自遥远地理位置的分离株，这表明抗原多样性存在局限性；然而，也观察到了人群和分离株之间的差异。许多妇女具有交叉反应性抗体和/或针对不同分离株的广泛抗体库。我们研究了 VAR2CSA 作为与胎盘结合分离株表达的主要抗原，确定了 DBL3 结构域中可变序列块编码的抗体表位。对全球 var2csa DBL3 序列的分析表明，非洲、亚洲、巴布亚新几内亚和拉丁美洲之间广泛共享可变块，这可能导致不同分离株之间存在高度的抗原重叠。然而，也有证据表明序列存在地理聚类和人群之间的 VAR2CSA 序列差异。研究结果表明，胎盘结合分离株的抗原多样性有限，这可能解释了为什么在一次妊娠中接触后可以获得妊娠期间对疟疾的免疫力。候选疫苗中包含有限数量的变体可能足以覆盖广泛的人群，但在疫苗设计中也可能需要考虑地理因素。
