Data from: A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies

<em>Streptococcus pneumoniae</em> (Spn) remains a major cause of global mortality, with extensive antigenic diversity between capsular serotypes that poses an ongoing challenge for vaccine development. Widespread use of pneumococcal conjugate vaccines (PCVs) targeting Spn capsules has greatly reduced infections by vaccine-included serotypes, but has led to increased infections by non-included serotypes. To date, high cost of PCVs has also limited their usefulness in low-income regions where disease burdens are highest. To overcome these limitations, serotype-independent vaccines are being actively researched. We have developed a whole-cell gamma-irradiated Spn vaccine (termed Gamma-PN) providing serotype-independent protection. We demonstrate that Gamma-PN immunization via the clinically relevant intramuscular route induces protein-specific antibodies able to bind numerous non-vaccine encapsulated serotypes, which mediate opsonophagocytic killing and protection against lethal challenges. Gamma-PN induced comparable or superior OPKA responses to serotypes found in the licensed Prevnar13 (PCV13), and a superior response to non-included serotypes, including emergent 22F and 35B. Additionally, despite a lower observed reactogenicity, administration of Gamma-PN without adjuvant resulted in higher OPKA responses and improved protection compared to adjuvanted Gamma-PN. To our knowledge, this has never been demonstrated for a whole-inactivated Spn vaccine. Eliminating the requirement for adjuvant comes with numerous benefits for clinical applications of this vaccine, and poses interesting questions for the inclusion of adjuvant in similar vaccines in development.肺炎链球菌（Streptococcus pneumoniae, Spn）仍是全球致死性疾病的主要病因，其荚膜血清型间存在广泛的抗原多样性，这为疫苗研发带来了持续挑战。目前，靶向Spn荚膜的肺炎球菌结合疫苗（pneumococcal conjugate vaccines, PCVs）的广泛应用已大幅降低了含疫苗血清型相关感染的发病率，但却导致非含疫苗血清型的感染率上升。迄今为止，PCVs的高昂成本也限制了其在疾病负担最重的低收入地区的推广应用。为克服这些局限，血清型非依赖性疫苗正被积极研究。本团队开发了一款全细胞γ辐照Spn疫苗（命名为Gamma-PN），可提供血清型非依赖性保护。研究证实，通过临床相关的肌内免疫途径接种Gamma-PN，可诱导产生蛋白特异性抗体，该抗体能够结合多种非疫苗覆盖的荚膜血清型，进而介导调理吞噬杀伤，并保护机体免受致死性感染攻击。Gamma-PN诱导的调理吞噬杀伤活性（opsonophagocytic killing assay, OPKA）应答水平与获批上市疫苗沛儿13（Prevnar13, PCV13）覆盖的血清型相当甚至更优，且对非覆盖血清型（包括新兴的22F和35B血清型）的应答水平更优。此外，尽管其观察到的反应原性（reactogenicity）更低，但与经佐剂（adjuvant）配制的Gamma-PN相比，接种无佐剂的Gamma-PN可诱导更高水平的OPKA应答，并带来更优的保护效果。据我们所知，目前尚无全灭活Spn疫苗被证实具备此类特性。取消佐剂需求可为该疫苗的临床应用带来诸多益处，同时也为同类在研疫苗是否添加佐剂的问题提供了新的研究思路。