Data from: Revaccination of cattle with Bacille Calmette-Guérin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis

In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 2½ years after vaccination and to determine the effect of revaccination after 2 years. Seventy–nine calves were divided into five groups (n = 15–17 calves/group) with four of the groups vaccinated subcutaneously with 105 CFU of BCG Danish at 2–4 weeks of age and the fifth group serving as non-vaccinated controls. Three of the four BCG-vaccinated groups were revaccinated 2 years after the initial vaccination. One BCG-vaccinated group was revaccinated with BCG. A second group was vaccinated subcutaneously with a TB protein vaccine consisting of biopolyester particles (Biobeads) displaying two mycobacterial proteins, ESAT-6 and Antigen 85A, mixed with an adjuvant. A third group was vaccinated with TB proteins from M. bovis culture filtrate, mixed with an adjuvant. Twenty-three weeks after the BCG revaccination, all animals were challenged endotracheally with virulent M. bovis and a further 13 weeks later, animals were killed and necropsied to determine protection against TB. The BCG-vaccinated animals produced positive tuberculin caudal fold intradermal (15 of 62 animals) and IFN-γ TB test responses (six of 62 animals) at 6 months after vaccination, but not at subsequent time-points compared to the non-vaccinated animals. Calves receiving a single vaccination with BCG vaccine 2½ years prior to challenge were not protected against TB, while those revaccinated with BCG 2 years after the initial vaccination displayed significant reductions in lung and pulmonary lymph node lesion scores compared to the non-vaccinated animals. In contrast, no reduction in lesion scores was observed in the animals revaccinated with the TB protein vaccines with their immune responses biased towards induction of antibody.针对人类与动物中，卡介苗（BCG vaccine）诱导的结核病（TB, Tuberculosis）保护持续时长，以及加强接种能否增强保护效果这两个问题，目前仍存在争议。本研究开展了一项长期试验，旨在明确接种卡介苗的犊牛在接种2.5年后，是否可抵御牛分枝杆菌（Mycobacterium bovis）攻毒，并探究初次接种2年后进行加强接种的效果。本研究将79头犊牛分为5组（每组15~17头）：其中4组于2~4周龄时皮下接种10^5菌落形成单位（CFU, Colony Forming Unit）的丹麦株卡介苗（BCG Danish），剩余1组作为非疫苗接种对照。4组卡介苗接种犊牛中的3组于初次接种后2年接受加强接种：1组使用卡介苗进行加强接种；1组皮下接种由包裹有两种分枝杆菌蛋白ESAT-6与抗原85A（Antigen 85A）的生物聚酯颗粒（Biobeads）搭配佐剂制成的结核病蛋白疫苗；1组使用牛分枝杆菌培养滤液中的结核蛋白搭配佐剂进行接种。剩余1组卡介苗接种犊牛仅接受单次卡介苗接种，未进行加强接种。在卡介苗加强接种后23周，对所有动物经气管内攻毒强毒牛分枝杆菌；再过13周后，剖杀所有动物并进行剖检，以评估其抗结核病保护效果。接种后6个月时，卡介苗接种动物的牛尾褶结核菌素皮内试验（tuberculin caudal fold intradermal test）阳性率为62头中的15头，干扰素γ（IFN-γ）结核病检测阳性率为62头中的6头；但与非接种组相比，后续时间点未出现此类阳性反应。攻毒前2.5年仅接受单次卡介苗接种的犊牛未表现出抗结核病保护效果；而初次接种2年后使用卡介苗加强的犊牛，其肺部及肺淋巴结病变评分较非接种组显著降低。与之相反，使用结核病蛋白疫苗进行加强接种的动物，病变评分未出现降低，且其免疫应答偏向于诱导抗体产生。