Overcoming Aging-Associated Poor Influenza Vaccine Responses with CpG 1018 Adjuvant

Abstract

Aging is associated with diminished immune system function, which renders old people vulnerable to influenza infection and also less responsive to influenza vaccination. This study explored whether the CpG 1018 adjuvant was effective in enhancing influenza vaccine efficacy in aged mice equivalent to human beings in their late 50s to early 60s. Using the influenza pandemic 2009 H1N1 (pdm09) vaccine as a model, we found that the CpG 1018 adjuvant could significantly enhance the pdm09 vaccine-induced serum antibody titer, while the pdm09 vaccine alone failed to elicit significant antibody titer. In contrast, the pdm09 vaccine alone elicited significant antibody titer in young adult mice. Antibody subtype analysis found that the pdm09 vaccine alone elicited Th2-biased antibody responses in young adult mice, while incorporation of the CpG 1018 adjuvant promoted the elicitation of potent Th1-biased antibody responses in aged mice. The pdm09 vaccine alone was further found to induce significant expansion of Th2 cells in young adult mice, while incorporation of the CpG 1018 adjuvant stimulated significant expansion of Th1 cells in aged mice. The CpG 1018 adjuvant also stimulated vaccine-specific cytotoxic T lymphocytes in aged mice. The pdm09 vaccine in the presence of CpG 1018 elicited significant protection against lethal viral challenges, while the pdm09 vaccine alone failed to confer significant protection in young adult or aged mice. Our study provided strong evidence to support the high effectiveness of the CpG 1018 adjuvant to boost influenza vaccination in aged mouse models.

A TLR9 agonist synergistically enhances protective immunity induced by an Alum-adjuvanted H7N9 inactivated whole-virion vaccine

“…Recent studies (Kang et al and Strohmeier et al) have reported the potential of using CpG 1018 as an effective adjuvant to enhance the efficacy of recombinant HA and NA vaccines [ 46 , 47 ]. However, the immunostimulatory effect of CpG adjuvant alone on influenza vaccines remains controversial.…”

“…Additionally, a clinical study revealed that 1 mg of CpG 7909 failed to improve humoral responses induced by a trivalent split influenza vaccine [ 29 ]. Kang et al reported the immune response induced by 0.5 μg of recombinant HA and 40 μg of CpG 1018, but this did not meet the common licensing criteria (HI titre of ≥ 40), and only a 40% survival rate was observed after adjuvanting with CpG 1018 [ 46 ]. On the other hand, Strohmeier et al showed that at least 3 μg of recombinant NA antigen was required when adjuvanted with CpG alone to induce robust protection against virus challenge in a mouse model [ 47 ].…”

Differential Regulation of DC Function, Adaptive Immunity, and MyD88 Dependence by Two Squalene Emulsion-Based Vaccine Adjuvants

“…A small volume of blood (~50 µL) was collected for measurement of serum antibody titer following procedures described in our previous reports [24,25]. In brief, 96-well plates were coated with 100 µg/mL OVA followed by blocking and incubation with 4-fold serial diluted serum samples.…”

Biomineralization-inspired synthesis of autologous cancer vaccines for personalized metallo-immunotherapy

“…CpG-ODN, a clinically approved Toll-like receptor 9 (TLR-9) agonist for cancer immunotherapy, was adopted as a positive control in this study due to its high capacity to facilitate the elicitation of cytotoxic T lymphocyte (CTL) immunological responses according to previous studies. 45 , 46 , 47 These mice received corresponding subcutaneous (s.c.) injections once a week three times, and the injection doses of OVA, Mn 2+ and CpG were 5.6 mg/kg, 1.5 mg/kg, and 1 mg/kg, respectively. ( Figure 4 A).…”