Gingerich Maria Cristina, Nair Nisha, Azevedo Jose F, Samanta Kamalika, Kundu Suman, He Biao, Gomes-Solecki Maria
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
CyanVac, LLC, Athens, GA, USA.
NPJ Vaccines. 2024 Feb 15;9(1):33. doi: 10.1038/s41541-023-00802-y.
Strategies for disease control are necessary to reduce incidence of Lyme Disease (LD) including development of safe vaccines for human use. Parainfluenza virus 5 (PIV5) vector has an excellent safety record in animals and PIV5-vectored vaccines are currently under clinical development. We constructed PIV5-vectored LD vaccine candidates expressing OspA from B. burgdorferi (OspA) and a chimeric protein containing sequences from B. burgdorferi and B. afzelii (OspA). Immunogenicity and vaccine efficacy were analyzed in C3H-HeN mice after prime-boost intranasal vaccination with live PIV5-OspA or PIV5-OspA, subcutaneous (s.c.) vaccination with rOspA+Alum, and the respective controls. Mice vaccinated intranasally with live PIV5-A or PIV5-A had higher endpoint titers of serum antibody against OspA at 6- and 12- months post vaccination, compared to mice vaccinated s.c. with rOspA. Neutralization activity of antibody was maintained up to 18-months post-immunization, with the response greater in live PIV5-delivered OspA vaccines, than that induced by s.c. rOspA. Challenge with infected ticks carrying 10-19 strains of B. burgdorferi performed at 4-, 9- or 15-months post-immunization showed increased breakthrough infections in mice vaccinated with s.c. rOspA compared to intranasal PIV5-A or PIV5-A at 9- and 15-months, as determined by quantification of serologic antibodies to B. burgdorferi proteins as well as flaB DNA in tissues, and by visualization of motile B. burgdorferi in culture of tissues under dark field microscope. These findings indicate that immunization of mice with PIV5 delivered OspA generates immune responses that produce longer-lasting protection ( > 1 year) against tick-transmitted B. burgdorferi than a parenteral recombinant OspA vaccine.
疾病控制策略对于降低莱姆病（LD）的发病率是必要的，包括开发用于人类的安全疫苗。副流感病毒5（PIV5）载体在动物中具有出色的安全记录，目前PIV5载体疫苗正在进行临床开发。我们构建了表达来自伯氏疏螺旋体（OspA）的OspA以及包含来自伯氏疏螺旋体和阿氏疏螺旋体序列的嵌合蛋白的PIV5载体LD疫苗候选物。在用活的PIV5 - OspA或PIV5 - OspA进行初免 - 加强鼻内接种、用重组OspA + 明矾进行皮下（s.c.）接种以及各自的对照后，在C3H - HeN小鼠中分析免疫原性和疫苗效力。与用重组OspA皮下接种的小鼠相比，在用活的PIV5 - A或PIV5 - A鼻内接种的小鼠在接种后6个月和12个月时具有更高的针对OspA的血清抗体终点滴度。抗体的中和活性在免疫后长达18个月都得以维持，活的PIV5递送的OspA疫苗诱导的反应比皮下重组OspA诱导的反应更大。在免疫后4个月、9个月或15个月用携带10 - 19株伯氏疏螺旋体的感染蜱进行攻毒显示，与9个月和15个月时鼻内接种PIV5 - A或PIV5 - A的小鼠相比，用重组OspA皮下接种的小鼠突破性感染增加，这通过对组织中针对伯氏疏螺旋体蛋白以及flaB DNA的血清学抗体进行定量以及通过在暗视野显微镜下观察组织培养中的活动伯氏疏螺旋体来确定。这些发现表明，用PIV5递送OspA免疫小鼠产生的免疫反应比肠胃外重组OspA疫苗对蜱传播的伯氏疏螺旋体产生更持久的保护（> 1年）。
