Morefield Garry L, Tammariello Ralph F, Purcell Bret K, Worsham Patricia L, Chapman Jennifer, Smith Leonard A, Alarcon Jason B, Mikszta John A, Ulrich Robert G
Department of Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
J Immune Based Ther Vaccines. 2008 Sep 3;6:5. doi: 10.1186/1476-8518-6-5.
Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy.
As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures.
The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B.
Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component.The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product.
联合疫苗减少了分别接种每种成分所需的注射总次数，并且通常提供相同水平的疾病保护。然而，疫苗成分之间的物理、化学和生物相互作用往往对疫苗安全性或效力有害。
作为联合疫苗的一种可能替代方案，我们使用专门设计的微针在恒河猴皮肤表面下方彼此相邻地注射四种分别用于炭疽、肉毒中毒、鼠疫和葡萄球菌中毒性休克的重组蛋白疫苗，从而避免潜在不相容的疫苗混合物。
皮内接种的疫苗保留了强大的抗体反应，并且恒河猴耐受性良好。基于佐剂追踪，疫苗通过抗原呈递细胞从真皮转运至引流淋巴结。接种疫苗的灵长类动物完全受到保护，免受炭疽芽孢杆菌孢子、肉毒杆菌神经毒素A或葡萄球菌肠毒素B的致死性气溶胶攻击。
我们的结果表明，疫苗在注射器中和给药部位的物理分离不会对每种成分的生物活性产生不利影响。我们描述的接种方法可能可扩展以纳入更多抗原，同时避免在一种产品中组合多种疫苗时遇到的物理和化学不相容性。
