Grimaldi Gabriel, Teva Antonio, Dos-Santos Claudiney B, Santos Fernanda Nunes, Pinto Israel de-Souza, Fux Blima, Leite Gustavo Rocha, Falqueto Aloísio
Instituto Gonçalo Moniz, Fiocruz, Salvador, Brazil, Brazil.
Escola Nacional de Saúde Pública, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.
PLoS One. 2017 Sep 27;12(9):e0185438. doi: 10.1371/journal.pone.0185438. eCollection 2017.
Because domestic dogs are reservoir hosts for visceral leishmaniasis (VL) in Brazil, one of the approaches used to reduce human disease incidence is to cull infected dogs. However, the results of controlled intervention trials based on serological screening of dogs and killing of seropositive animals are equivocal. A prophylactic vaccine to protect dogs from being infectious to the sand fly vector could be an effective strategy to provide sustained control. Here, we investigated whether a currently licensed commercial subunit rA2 protein-saponin vaccine (Leish-tec®) had an additional effect to dog culling on reducing the canine infectious populations.
METHODOLOGY/PRINCIPAL FINDINGS: This prospective study was conducted in an L. infantum highly endemic area of southeast Brazil. At the onset of the intervention, all of the eligible dogs received through subcutaneous route a three-dose vaccine course at 21-day intervals and a booster on month 12. For the purpose of comparison, newly recruited healthy dogs were included as the exposed control group. To ascertain vaccine-induced protection, dogs were screened on clinical and serological criteria every 6 months for a 2-year follow-up period. Antibody-based tests and histopathological examination of post-mortem tissue specimens from euthanized animals were used as a marker of infection. The standardized vaccine regime, apart from being safe, was immunogenic as immunized animals responded with a pronounced production of anti-A2-specific IgG antibodies. It should be noted the mean seroconversion time for infection obtained among immunized exposed dogs (~ 18 months), which was twice as high as that for unvaccinated ones (~ 9 months). After two transmission cycles completed, the cumulative incidence of infection did differ significantly (P = 0.016) between the vaccinated (27%) and unvaccinated (42%) dogs. However, the expected efficacy for the vaccine in inducing clinical protection was not evident since 43% of vaccine recipients developed disease over time. Our estimates also indicated that immunoprophylaxis by Leish-tec® vaccine in addition to dog culling might not have an impact on bringing down the incidence of canine infection with L. infantum in areas of high transmission rates.
CONCLUSIONS/SIGNIFICANCE: Leish-tec® as a prophylactic vaccine showed promise but needs to be further optimized to be effective in dogs under field conditions, and thereby positively impacts human incidence.
由于家犬是巴西内脏利什曼病（VL）的储存宿主，降低人类疾病发病率的一种方法是扑杀感染的犬只。然而，基于犬只血清学筛查和扑杀血清阳性动物的对照干预试验结果并不明确。一种预防性疫苗，可保护犬只不感染白蛉媒介，可能是提供持续控制的有效策略。在此，我们研究了目前已获许可的商业亚单位rA2蛋白-皂苷疫苗（Leish-tec®）在减少犬类感染群体方面，除犬只扑杀外是否具有额外效果。
方法/主要发现：这项前瞻性研究在巴西东南部婴儿利什曼原虫高度流行地区进行。干预开始时，所有符合条件的犬只通过皮下途径每隔21天接受三剂疫苗接种，并在第12个月进行一次加强接种。为作比较，新招募的健康犬只被纳入暴露对照组。为确定疫苗诱导的保护作用，在为期2年的随访期内，每6个月根据临床和血清学标准对犬只进行筛查。基于抗体的检测以及对安乐死动物的死后组织标本进行组织病理学检查，用作感染的标志物。标准化疫苗接种方案除安全外，还具有免疫原性，因为免疫动物产生了大量抗A2特异性IgG抗体。应当注意的是，免疫暴露犬只中感染的平均血清转化时间（约18个月），是未接种疫苗犬只（约9个月）的两倍。在完成两个传播周期后，接种疫苗（27%）和未接种疫苗（42%）的犬只之间感染的累积发病率存在显著差异（P = 0.016）。然而，疫苗诱导临床保护的预期效果并不明显，因为随着时间推移，43%的疫苗接种者发病。我们的估计还表明，在高传播率地区，除犬只扑杀外，使用Leish-tec®疫苗进行免疫预防可能对降低犬只感染婴儿利什曼原虫的发病率没有影响。
结论/意义：Leish-tec®作为一种预防性疫苗显示出前景，但需要进一步优化，以便在野外条件下对犬只有效，从而对人类发病率产生积极影响。
