Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA.
Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.
mSphere. 2024 Nov 21;9(11):e0064724. doi: 10.1128/msphere.00647-24. Epub 2024 Oct 23.
Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination. These increases are attributed to the reduced protection against colonization, carriage, and transmission as well as reduced duration of immunity conferred by aP vaccines relative to the wP vaccines they replaced. A reduced reactogenicity whole-cell pertussis (RRwP) vaccine was recently developed with the goal of achieving the same protection as conferred by wP vaccination but with an improved safety profile, which may benefit countries in which wP vaccines are still in routine use. In this study, we tested the RRwP vaccine in a baboon model of pertussis infection. We found that the RRwP vaccine induced comparable cellular and humoral immune responses and comparable protection following challenge relative to the wP vaccine, while significantly reducing injection-site reactogenicity.IMPORTANCEThe World Health Organization (WHO) recommended in 2015 that countries administering wP vaccines in their national vaccine programs should continue to do so, and that switching to aP vaccines for primary infant immunization should only be considered if periodic booster vaccinations and/or maternal immunization could be assured and sustained in their national immunization schedules (WHO, Vaccine 34:1423-1425, 2016, https://doi.org/10.1016/j.vaccine.2015.10.136). Due to the considerably higher cost of aP vaccines and the larger number of doses required, most LMICs continue to use wP vaccines. The development and introduction of a wP vaccine that induces fewer adverse events without sacrificing protection would significantly benefit countries in which wP vaccines are still in routine use. The results of this study indicate this desirable goal may be achievable.
全细胞百日咳（wP）疫苗于 20 世纪 40 年代问世，大幅降低了百日咳的发病率，目前仍在全球范围内的中低收入国家（LMICs）广泛使用。wP 疫苗的不良反应降低了其公众接受度，这促使高收入国家在 20 世纪 90 年代开发并引入了无细胞百日咳（aP）疫苗。尽管儿童接种率接近普及，但高收入国家在引入 aP 疫苗后，百日咳疾病的发病率有所上升。这归因于 aP 疫苗相对于其替代的 wP 疫苗，对定植、携带和传播的保护作用降低，以及免疫持续时间缩短。最近开发了一种减毒全细胞百日咳（RRwP）疫苗，其目标是实现与 wP 疫苗相同的保护效果，但具有更好的安全性，这可能使仍在常规使用 wP 疫苗的国家受益。在这项研究中，我们在百日咳感染的狒狒模型中测试了 RRwP 疫苗。我们发现，RRwP 疫苗在诱导细胞和体液免疫应答以及在接种后提供保护方面与 wP 疫苗相当，而注射部位不良反应明显减少。
重要性
世界卫生组织（WHO）在 2015 年建议，在国家疫苗计划中使用 wP 疫苗的国家应继续使用该疫苗，如果周期性加强免疫接种和/或在国家免疫计划中可以保证和持续使用母亲免疫接种，才应考虑将 aP 疫苗用于婴幼儿初级免疫接种（WHO，Vaccine 34：1423-1425，2016，https://doi.org/10.1016/j.vaccine.2015.10.136）。由于 aP 疫苗的成本高得多，所需剂量也多，因此大多数中低收入国家仍在使用 wP 疫苗。开发和引入一种不良反应更少但不牺牲保护作用的 wP 疫苗，将使仍在常规使用 wP 疫苗的国家显著受益。本研究的结果表明，这一理想目标可能是可以实现的。
