Effective adjuvantation of nanograms of influenza vaccine and induction of cross-protective immunity by physical radiofrequency adjuvant

Abstract

Novel adjuvants are highly demanded to aid in development of improved or new vaccines against existing or emerging infectious diseases. Considering commonly used Alum and MF59 adjuvants induce tissue stress and release of endogenous danger signals to mediate their adjuvant effects, physical modalities may be used to induce tissue stress and endogenous danger signal release to enhance vaccine-induced immune responses. Furthermore, physical adjuvants are less likely to induce significant systemic adverse reactions due to their localized effects. Recently we found non-invasive radiofrequency (RF) pretreatment of the skin could significantly enhance intradermal vaccine-induced immune responses in murine models that included pandemic influenza vaccine, pre-pandemic vaccine, and influenza internal antigen vaccine. It remained to be explored whether the physical RF adjuvant (RFA) could be used to boost seasonal influenza vaccination, spare vaccine doses, and induce cross-protective immunity. This study found the physical RFA could significantly enhance seasonal influenza vaccine-induced immune responses against each viral strain and robustly enhance low-dose (nanograms) H3N2 vaccine-induced immune responses and protection in murine models. RFA also induced cross-protective immunity against heterologous and heterosubtypic influenza viruses. Further studies found heat shock protein 70 (inducible endogenous danger signal) and myeloid differentiation primary response 88 adaptor played a crucial role in dose-sparing effects of RFA. These data strongly support further development of the physical RFA to boost influenza vaccination.

Emerging adjuvants for intradermal vaccination

“…The superior RFA effects at low vaccine doses hinted its excellent dose-sparing effects. In support, we found RFA could adjuvant nanograms of H3N2 vaccine to induce potent immune responses and protection in murine models ( Li et al, 2022 ). Considering the prior laser adjuvant effects were primarily compared with the relatively weak Alum adjuvant, RFA represented the first physical adjuvant that showed comparable adjuvant effects to the most widely used chemical adjuvant (MF59-like AddaVax) to boost influenza vaccination.…”

“…RFA showed a similar adjuvant effect to AddaVax in boosting intradermal NP/M1 immunization ( Li et al, 2021 ). RFA was recently found to also broaden influenza vaccine-induced immune responses against heterologous viruses ( Li et al, 2022 ). The induction of cross-protective immunity was likely to be due to its induction of cross-protective cytotoxic T lymphocytes ( Li et al, 2022 ).…”

CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein

“…Animal experiments were approved by the Institutional Animal Care and Use Committee of University of Rhode Island (URI) with approval #AN1516–004. Male C57BL/6 mice (6–8 weeks old, Jackson Laboratories) were subjected to hair removal on the lateral back skin one day before experiment as in our previous report [ 21 ]. Mice were intradermally injected with 5 μg rNP (endotoxin level < 50 EU per mg of protein) alone or in the presence of 40 μg CpG 1018 [ 22 ], or intradermally injected with PBS, or intramuscularly injected with 5 μg rNP admixed with AddaVax (1:1 volume ratio).…”

Selenium and zinc alleviate hepatotoxicity induced by heavy metal mixture (cadmium, mercury, lead and arsenic) via attenuation of inflammo‐oxidant pathways

“…At the end of the experiment (day 60), animals were sacrificed under ketamine (80 mg/kg) anesthesia 21 . Blood samples were collected following cardiac puncture and stored in plain bottles.…”

“…At the end of the experiment (day 60), animals were sacrificed under ketamine (80 mg/kg) anesthesia. 21…”