In newborns, respiratory syncytial virus (RSV) is a significant respiratory infection. The early formalin-inactivated RSV not only failed to protect newborns from infection, but it was also linked to increased pulmonary inflammatory illness after spontaneous infection. A safe and effective vaccination should both prevent and protect against the inflammatory illness. Vaccines rely heavily on immune memory. Researchers tested three types of immune memory T cells, antibodies, and lung inflammation using intranasal (i.n.) and intraperitoneal (i.p.) immunization protocols with a vaccine candidate G1F/M2, which includes a neutralizing epitope fragment of RSV G protein and a cytotoxic T lymphocyte epitope of M2 protein, with toll-like receptor 9 agonist CpG2006 as an adjuvant. The results showed that immunization with G1F/M2 + CpG i.p. induced significantly higher levels of CD4+ or CD8+ central memory (TCM), Th1-type effector memory (TEM), and a balanced ratio of IgG1/IgG2a, but a lower level of lung tissue-resident memory (TRM) than immunization with G1F/M2 i.n., G1F/M2 i.p. Following RSV challenge, animals vaccinated with G1F/M2 + CpG i.p. had greater levels of Th1-type responses, significantly reduced inflammatory cytokines, and improved lung histology compared to mice inoculated with G1F/M2 i.n., G1F/M2 i.p., or G1F/M2 i.n.

These findings showed that a high level of TCM and Th1-type TEM in the spleens may contribute to the prevention of lung inflammation, whereas a high level of TRM in the lungs and a lack of or weak Th1-type immunological memory in the spleens may increase lung inflammation.