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Background The aim of the current study was to determine the safety and immunogenicity of trivalent inactivated influenza vaccine (TIV) alone or formulated with Advax delta inulin adjuvant in those who were older (aged >60 years) or had chronic disease. Methods Over 4 consecutive years from 2008 through 2011, adult participants with chronic disease or >60 years of age were recruited into a randomized controlled study to assess the safety, tolerability and immunogenicity of Advax-adjuvanted TIV (TIV + Adj) versus standard TIV. The per-protocol population with ≥1 postbaseline measurement of influenza antibodies comprised 1297 participants, 447 in the TIV and 850 in the TIV + Adj) group. Results No safety issues were identified. Variables negatively affecting vaccine responses included obesity and diabetes mellitus. Advax adjuvant had a positive impact on anti-influenza immunoglobulin M responses and on H3N2 and B strain seropositivity as assessed by hemagglutination inhibition. Conclusions TIV + Adj was safe and well tolerated in individuals with chronic disease. There is an ongoing need for research into improved influenza vaccines for high-risk populations. Clinical Trials Registration Australia New Zealand Clinical Trial Registry: ACTRN 12608000364370. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can infect a broad range of animal species and has been associated with severe disease in some taxa. Few studies have evaluated optimal strategies to mitigate the risk to susceptible zoo animals. This study evaluated the safety and immunogenicity of a protein‐based veterinary SARS‐CoV‐2 vaccine (SpikeVet™) in zoo animals. Two to three doses of SpikeVet™ were administered intramuscularly or subcutaneously 3–4 weeks apart to 354 zoo animals representing 38 species. SpikeVet™ was very well tolerated across all species. Minor adverse effects were observed in 1.69% of animals vaccinated, or 1.04% of vaccine doses administered. Preliminary immunogenicity analyses in representative carnivores (meerkats, lions) and an artiodactylid (domestic goat) showed SpikeVet™‐immunized animals developed serum antibodies able to neutralize a range of SARS‐CoV‐2 variants, including the vaccine‐homologous Wuhan and Mu variants, as well as vaccine‐heterologous Omicron BA.2 and XBB.1 strains. Prior to vaccination, all eight lions were seropositive for Wuhan strain by surrogate viral neutralization testing, suggesting past infection with SARS‐CoV‐2 or cross‐reactive antibodies generated by another closely related coronavirus. These results from a range of zoo species support the ongoing development of SpikeVet™ as a safe and effective veterinary SARS‐CoV‐2 vaccine. [ABSTRACT FROM AUTHOR]

SpikoGen® vaccine is a subunit COVID‐19 vaccine expressed in insect cells comprising recombinant spike protein extracellular domain formulated with Advax‐CpG55.2™ adjuvant. A Phase 2 trial was conducted in 400 adult participants randomised 3:1 to receive two intramuscular doses of SpikoGen® vaccine or saline placebo 3 weeks apart. Some Phase 2 trial participants later enrolled in a separate booster study and received a third dose of SpikoGen® vaccine. This stored serum was used to assess the ability of SpikoGen® vaccine to induce cross‐neutralising antibodies against SARS‐CoV‐2 variants of concern. Sera taken at baseline and 2 weeks after the second vaccine dose from baseline seronegative Phase 2 subjects was evaluated using a panel of spike pseudotype lentivirus neutralisation assays for the ability to cross‐neutralise a wide range of SARS‐CoV‐2 variants, including Omicron BA.1, BA.2 and BA.4/5. Stored samples of subjects who participated in both the 2‐dose Phase 2 trial and a third dose booster trial 6 months later were also analysed for changes in cross‐neutralising antibodies over time and dose. Two weeks after the second dose, sera broadly cross‐neutralised most variants of concern, albeit with titres against Omicron variants being ~10‐fold lower. While Omicron titres fell to low levels 6 months after the second vaccine dose in most subjects, they showed a ~20‐fold rise after the third dose booster, after which there was only a ~2‐3‐fold difference in neutralisation of Omicron and the ancestral strains. Despite being based on the ancestral Wuhan sequence, after two doses, SpikoGen® vaccine induced broadly cross‐neutralising serum antibodies. Titres then reduced over time but were rapidly restored by a third dose booster. This resulted in high neutralisation including against the Omicron variants. This data supports ongoing use of SpikoGen® vaccine for protection against recent SARS‐CoV‐2 Omicron variants. [ABSTRACT FROM AUTHOR]

TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure-function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation. In this work, we sought to address this issue through structural modifications in the agonists to enhance their adsorption capacity to the classic adjuvant alum. We selected a potent TLR7-selective agonist, BBIQ (EC 50 = 0.85 μM), and synthesized polyphenolic derivatives to assess their TLR7 agonistic activity and adjuvant potential alone or in combination with alum. Most of the phenolic derivatives were more active than BBIQ and, except for 12b , all were TLR7 specific. Although the synthesized compounds were less active than resiquimod, the immunization data on combination with alum, specifically the IgG1, IgG2b and IgG2c responses, were superior in comparison to BBIQ as well as the reference standard resiquimod. Compound 12b was 5-fold more potent (EC 50 = 0.15 μM in TLR7) than BBIQ and induced double the IgG response to SARS-CoV-2 and hepatitis antigens. Similarly, compound 12c (EC 50 = 0.31 μM in TLR7) was about 3-fold more potent than BBIQ and doubled the IgG levels. Even though compound 12d exhibited low TLR7 activity (EC 50 = 5.13 μM in TLR7), it demonstrated superior adjuvant results, which may be attributed to its enhanced alum adsorption capability as compared with BBIQ and resiquimod. Alum-adsorbed polyphenolic TLR7 agonists thereby represent promising combination adjuvants resulting in a balanced Th1/Th2 immune response., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Lipopeptides including diacylated Pam 2 CSK 4 as well as triacylated Pam 3 CSK 4 act as ligands of toll-like receptor (TLR)-2, a promising target for the development of vaccine adjuvants. The highly investigated Pam 2 CSK 4 and Pam 3 CSK 4 , despite their aqueous solubility have not performed well as vaccine adjuvants which may be attributable to potential denaturation of protein antigens by these cationic surfactant-like lipopeptides. In the present investigation, we synthesized ( R ), ( S ) and racemic Pam 2 CS(OMe) analogs and their N -acetyl derivatives without the tetralysine component to systematically investigate the effect of stereochemistry at the thio-glycerol lipopeptide core of these lipopeptide based TLR2 agonists. The resulting compounds were compared using TLR2 reporter cell-based assays and the ability of the synthesized lipopeptides to stimulate cytokine production (IL-6, IL-10 and TNF-α) by freshly collected human PBMCs and CD40 and CD86 expressions by mouse spleen cells was also investigated. Notably, few synthesized lipopeptides were found to be potent TLR2/6 agonists, inducing cytokine production and upregulating CD40 and CD86 expressions. The TLR2/6 agonistic lipopeptides were further assessed for vaccine adjuvant effects in mice. The results confirmed that the R -stereochemistry at the thio-glycerol lipopeptide core was preferred for maximal TLR2/6 activity, as reflected in Th1 immune deviation, higher antibody levels and enhanced vaccine protection against a lethal influenza challenge., Competing Interests: There is no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)