Christensen N D, Reed C A, Cladel N M, Han R, Kreider J W
Department of Pathology, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
J Virol. 1996 Feb;70(2):960-5. doi: 10.1128/JVI.70.2.960-965.1996.
Rabbits were immunized with recombinant baculovirus-produced virus-like particles (VLPs) of cottontail rabbit papillomavirus (CRPV) to determine whether these antigens could induce long-term protection against experimental challenge with CRPV. Infectious CRPV and human papillomavirus type 11 L1 VLPs were used as positive and negative control immunogens, respectively. Three groups of immunized animals were challenged with 10-fold serial dilutions of infectious CRPV at 2 weeks, 6 months, and 12 months after immunizations. Antibody titers in serum reached 1:10,000 immediately after the final booster immunization and then decayed to 1:150 at 6 months and 1:100 at 12 months in unchallenged rabbits. Serum neutralization titers followed similar kinetics. Papillomas grew on control-immunized rabbits at sites challenged with 10(-1) (100% of sites), 10(-2) (96% of sites), 10(-3) (63% of sites), and 10(-4) (13% of sites) dilutions of virus. At 2 weeks after CRPV L1 VLP immunizations, the rabbits were completely protected against virus challenge. At both 6 and 12 months after CRPV L1 VLP immunizations, strong protection was also observed. In the last two groups, three of seven rabbits were completely protected and only 4 of 14 or 29% of sites challenged with 10(-1 dilution of virus grew papillomas. Papillomas growing at these four sites were also reduced in size (3.5 +/- 0.7 mm) at 50 days postchallenge compared with sites challenged with 10(-1) dilution on control-immunized rabbits (13.2 +/- 4.2 mm). The results demonstrate that strong and long-lasting protection against experimental challenge with papillomaviruses can be achieved with VLP immunogens.
用重组杆状病毒产生的棉尾兔乳头瘤病毒（CRPV）样病毒颗粒（VLPs）免疫兔子，以确定这些抗原是否能诱导对CRPV实验性攻击的长期保护。分别使用感染性CRPV和11型人乳头瘤病毒L1 VLPs作为阳性和阴性对照免疫原。三组免疫动物在免疫后2周、6个月和12个月用10倍系列稀释的感染性CRPV进行攻击。在最后一次加强免疫后，未受攻击的兔子血清中的抗体滴度立即达到1:10,000，然后在6个月时降至1:150，在12个月时降至1:100。血清中和滴度遵循相似的动力学。在接受10⁻¹（100%的部位）、10⁻²（96%的部位）、10⁻³（63%的部位）和10⁻⁴（13%的部位）稀释病毒攻击的对照免疫兔子的部位上长出了乳头瘤。在CRPV L1 VLP免疫后2周，兔子对病毒攻击完全有保护作用。在CRPV L1 VLP免疫后6个月和12个月时，也观察到了强大的保护作用。在最后两组中，七只兔子中有三只得到了完全保护，在用10⁻¹稀释病毒攻击的部位中，只有14个部位中的4个（或29%）长出了乳头瘤。与对照免疫兔子用10⁻¹稀释病毒攻击的部位（13.2±4.2毫米）相比，在攻击后50天，在这四个部位长出的乳头瘤大小也减小了（3.5±0.7毫米）。结果表明，用VLP免疫原可以实现对乳头瘤病毒实验性攻击的强大而持久的保护。
