Bandim Health Project, Department of Clinical Research, University of Southern Denmark, Copenhagen, Denmark; Copenhagen Phase IV Unit, Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark; Department of Health Technology, Technical University of Denmark, Kgs Lyngby, Denmark.
SEGES Danish Pig Research Centre, Copenhagen, Denmark.
Vaccine. 2022 Mar 8;40(11):1665-1673. doi: 10.1016/j.vaccine.2021.03.083. Epub 2021 Apr 9.
Human non-live vaccines have been associated with detrimental non-specific effects (NSE), particularly in females. A large trial found 2-fold increased overall mortality in girls receiving a new malaria vaccine compared to the rabies vaccine used as a coontrol; a beneficial NSE of the rabies vaccine was proposed. Conversely, in dogs increased mortality was seen in females but not males following rabies vaccination of puppies born to immunized mothers. We investigated NSE of non-live rabies vaccine in piglets and the potential modifying effect of maternal priming with rabies vaccine.
In a Danish herd of commercial rabies virus-free pigs, 575 pregnant sows (2-3 weeks before scheduled farrowing) and 5747 of their offspring (median 6-day-old) were allocated (1:1) to non-live rabies vaccine (Versiguard rabies vet) or no rabies vaccine. Outcomes were overall mortality and antibiotic treatment until departure from the nursery (approximately age 12 weeks/30 kgs).
Until weaning, overall offspring mortality was 2.2% (127 piglets died, rabies vaccine: n = 69; control: n = 58), the proportion ratio (PR) being 1.19 (95% confidence interval: 0.84-1.68). Until end of follow-up, mortality was 4.1% (233, rabies vaccine: n = 115; control = 118, PR: 0.97 (0.76-1.25)). Prior sow rabies vaccination did not affect piglet mortality. For mortality as well as risk of antibiotic treatment before weaning, there was indication of a beneficial effect of rabies vaccine in female piglets, but a negative effect in (castrated) male piglets from rabies-naïve sows. Prior sow vaccination significantly modified the vaccine effect estimate in female piglets toward a detrimental effect of rabies vaccine on treatment risk. These effects had waned by 12 weeks of age.
The study did not support the hypothesized beneficial NSE of rabies vaccine. Although under-powered for subgroup analyses, the study indicated effect modification by sex and maternal vaccination. Results could be different in a herd with higher mortality and infectious burden.
人类非活疫苗与有害的非特异性效应（NSE）有关，尤其是在女性中。一项大型试验发现，与用作对照的狂犬病疫苗相比，接受新疟疾疫苗的女孩的总死亡率增加了一倍；提出了狂犬病疫苗的有益 NSE。相反，在小狗中，在免疫母亲所生的小狗接受狂犬病疫苗接种后，雌性的死亡率增加，但雄性没有。我们研究了非活狂犬病疫苗在仔猪中的 NSE 作用，以及狂犬病疫苗母体致敏的潜在修饰作用。
在丹麦一个无狂犬病病毒的商业猪群中，575 头妊娠母猪（在预定分娩前 2-3 周）及其 5747 头仔猪（中位数为 6 天大）被分配（1:1）接受非活狂犬病疫苗（Versiguard 狂犬病疫苗）或不接受狂犬病疫苗。结果是总死亡率和从保育室（约 12 周龄/30 公斤）离开前的抗生素治疗。
在断奶前，仔猪的总死亡率为 2.2%（127 头仔猪死亡，狂犬病疫苗：n=69；对照组：n=58），比例比（PR）为 1.19（95%置信区间：0.84-1.68）。在随访结束时，死亡率为 4.1%（233 头，狂犬病疫苗：n=115；对照组 118，PR：0.97（0.76-1.25））。母猪先前接种狂犬病疫苗不会影响仔猪的死亡率。对于断奶前的死亡率和抗生素治疗风险，狂犬病疫苗对雌性仔猪有有益作用的迹象，但对来自狂犬病未感染母猪的（去势）雄性仔猪有负面影响。母猪先前的疫苗接种显著改变了雌性仔猪的疫苗效果估计值，使狂犬病疫苗对治疗风险产生有害影响。这些影响在 12 周龄时已经减弱。
该研究不支持狂犬病疫苗假设的有益 NSE。尽管亚组分析的效力不足，但该研究表明了性别和母体疫苗接种的效应修饰。在死亡率和传染性负担较高的畜群中，结果可能会有所不同。
