Biology subjects

Wong, P. T.

Publications and source records attributed to Wong, P. T..

6 recordsLinked to original sources

bioRxiv2026

Evaluation of new adjuvants in enhancing the immune response to a candidate of Severe Fever with Thrombocytopenia Syndrome Virus vaccine.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne bunyavirus SFTSV. SFTSV is primarily transmitted by Haemaphysalis longicornis ticks and can cause a hemorrhagic fever-like illness characterized by high fever, thrombocytopenia, leukopenia, and multiorgan failure, with reported case-fatality rates ranging from 10% to over 30%. Despite its growing public health relevance, no licensed vaccines or specific antiviral therapies are currently available. Here, we evaluated a beta-propiolactone-inactivated SFTSV vaccine candidate based on strain YL1, formulated with benchmark adjuvants (Addavax and Alhydrogel) or experimental innate immune agonists, including Sendai virus-derived defective interfering RNA (SDI), a RIG-I agonist, and imidazoquinoline-poly(ethylene glycol)-cholesterol conjugate (IMDQ-P-C), a TLR7/8 agonist, alone or in combination. Using an extended prime-boost regimen, we examined adjuvant-dependent modulation of humoral immunity, antigen-specific cellular recall, antibody cross-reactivity, and functional protection following passive serum transfer and live-virus challenge in IFNAR-/- mice. All adjuvanted formulations induced detectable humoral responses, with Addavax and SDI eliciting the highest virus-specific binding and neutralizing antibody titers. Antigen-specific analyses identified the nucleoprotein (NP) as the dominant target of vaccine-induced immune memory. NP elicited robust antibody response and the broadest cytokine recall profile following ex vivo stimulation. This response was broader than that induced by the whole inactivated virus and was characterized by mixed Th1-associated, Th2-associated, and proinflammatory-associated features that varied across adjuvant formulations. In contrast, the head domain of the Gn glycoprotein elicited limited cellular recall responses, consistent with its relatively weak humoral immunogenicity after both priming and boosting. Nevertheless, sera from SDI and Addavax-adjuvanted groups displayed cross-reactivity with Gn from a heterologous SFTSV strain, suggesting broader antibody recognition across viral genotypes. Functionally, sera from SDI and Addavax-immunized mice conferred partial protection following passive transfer into IFNAR-/- recipients, as reflected by reduced viral loads, delayed disease onset, and prolonged survival after lethal SFTSV challenge. Together, these findings support the immunogenicity and protective potential of a BPL-inactivated SFTSV vaccine platform and identify NP as a major target of vaccine-induced immune memory. They further highlight the importance of adjuvant selection in shaping the magnitude, antigenic focus, and functional quality of vaccine-induced antiviral immunity.

microbiology↗

bioRxiv2026

Adjuvanted mucosal vaccination enhances protection and prevents influenza virus transmission in the guinea pig model.

Influenza virus infects the respiratory mucosa, highlighting the importance of mucosal immunity for early protection and transmission control. Here, we evaluated whether intranasal (IN) vaccination with recombinant trimeric hemagglutinin protein from A/Michigan/45/2015 (triHA) formulated with a combined mucosal adjuvant, nanoemulsion plus IVT, an RNA-based RIG-I agonist (NE/IVT), could protect guinea pigs against heterologous A/Netherlands/602/2009 challenge and reduce viral transmission. To compare mucosal and parenteral immunization, IN triHA/NE/IVT was benchmarked against IN triHA alone, IM triHA/AddaVax (IM triHA/Advx), and standard IM quadrivalent inactivated influenza vaccine (QIV). We also tested whether IN triHA/NE/IVT could boost IM QIV- primed immunity and included animals previously infected with A/Michigan/45/2015 to model pre-existing infection- induced immunity. Transmission was assessed by co-housing naive sentinels with vaccinated, challenged donors. IN triHA/NE/IVT induced systemic humoral responses comparable to IM triHA/Advx while generating superior nasal mucosal IgA responses. Unexpectedly, IM triHA/AddaVax also induced detectable, albeit lower, mucosal IgG and IgA, contrasting with prior mouse data and highlighting species-specific differences. IN triHA/NE/IVT boosting after IM QIV enhanced serum IgG and mucosal IgA compared with QIV prime-boost alone and increased cross-neutralizing activity against antigenically distinct A/Victoria/4897/2022. Both IN triHA/NE/IVT and IN Michigan/15 prior- infection prevented detectable viral shedding after challenge, and naive sentinels co-housed with IN triHA/NE/IVT- vaccinated donors remained seronegative. Together, these findings support NE/IVT as a potential mucosal platform capable of inducing robust systemic and mucosal immunity and boosting IM vaccine-primed responses.

microbiology↗

bioRxiv2026

Intranasal Delivery of HIV/SIV Antigens with NE/AS01B Adjuvants Enhances Cellular Immunity and Reduces Viral Loads in SHIV-Challenged Macaques

The primary route of HIV transmission is across mucosal tissues; therefore, developing a protective mucosal vaccine is a top priority. In a pilot study, using a macaque model, we delivered HIV gp140 envelope glycoprotein and SIVmac239 P55 Gag and Nef antigens using heterologous prime/boost via the intranasal route with a soybean oil-based nanoemulsion (NE) adjuvant and through the intramuscular route with the AS01B adjuvant system to generate enhanced cell-mediated immunity. We used a NE adjuvant to promote gut-homing cell-mediated immunity and the AS01B system to enhance humoral immune responses. Following intrarectal challenge with SHIV 4MTF.tHy, vaccinated macaques acquired the virus but experienced lower viral loads in plasma (P=0.003) and CSF (P=0.001), and potent polyfunctional gag-specific (CD107a+, IFN{gamma}, TNF+) responses across diverse lymph nodes. Significant antibody-dependent complement deposition (ADCD) and antibody-dependent cellular phagocytosis (ADCP) responses were induced, and gut-microbiome crosstalk could be modulated and showing reduced SHIV-dysbiosis. Notably, vaccination preserved mucosal all-trans retinoic acid levels (atRA) (p<0.05). However, no significant differences were observed for antibody responses between vaccinated and unvaccinated macaques. In summary, the induced gut-homing properties by the NE adjuvant are effective at generating cell-mediated immunity and reducing viral set points and warrant further investigations as a mucosal adjuvant in HIV vaccine design. ImportanceThree major non-mucosal vaccine trials (RV144, HVTN702, and 706) failed to reduce HIV infection rates. Therefore, new approaches in developing a mucosal vaccine remain an effective strategy to attempt to control HIV infection. Coherent vaccine approaches against HIV were focused on immune correlates related to viral loads, persistent reservoirs, and antibody responses. As a proof-of-principle, we developed a vaccine regimen consisting of AS01B and an adjuvanted oil-in-water NE cleaved HIV clade C gp140 protein and non-cleaved Gag, and nef particles administered through intranasal, subcutaneous, and intramuscular routes, followed by intrarectal challenge with clade C SHIV. This vaccine elicited strong ADCD and ADCP responses, modulated immune-microbiome crosstalk, and reduced susceptibility to SHIV-infection-associated dysbiosis. Additionally, it preserved mucosal all trans retinoic acid (atRA) levels, suggesting a potential role for this approach in HIV vaccine development.

microbiology↗

bioRxiv2025

A combination TLR7/8 and RIG-I agonist adjuvant reverts asthmatic allergic sensitization and prevents aggravated influenza infection in OVA-sensitized mice.

Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment currently available to treat allergy. However, it has limitations, as most allergens are poorly immunogenic, resulting in an AIT process that can take years. Therefore, adjuvant selection becomes critical to achieve a more efficacious therapy. Our group has developed and tested an amphiphilic TLR7/8 agonist (IMDQ) and a RIG-I agonist (SDI) that used alone, or in combination, have demonstrated strong adjuvant activity for influenza and SARS-CoV-2 vaccines in preclinical models. Here we describe the effect of these adjuvants in the sensitization of preclinical models with the ovalbumin (OVA) asthmatic allergic model via an in-depth humoral and cellular immune profiling. We assess their immune skewing and tolerance inducing capacities in previously sensitized preclinical models with different genetic backgrounds (C57BL/6 vs. BALB/c mice). Moreover, we evaluate their effect in an unrelated antigenic challenge with influenza. Finally, we investigate the role of IgG subclasses and T-cell subpopulations in the protection against OVA challenge conferred by the combination of IMDQ and SDI. We demonstrate that OVA-immunization in combination with IMDQ+SDI prevents allergic sensitization via the induction of a balanced Type 1/Type 2 response. Furthermore, it can revert the allergic phenotype in mice previously sensitized with OVA-Alum, through reducing lung eosinophilia, as well as IL-4 and IL-5 production. However, this was dependent on genetic background. IMDQ+SDI sensitization also led to reduced morbidity of a secondary influenza challenge in OVA-sensitized mice. Finally, we demonstrated that IgG2c, by itself, cannot protect from allergic sensitization and that both CD4+ and CD8+ T-cells are needed for IMDQ+SDI prevention of eosinophil recruitment and activation upon intranasal OVA-challenge.

immunology↗

bioRxiv2024

Enhanced mucosal B- and T-cell responses against SARS-CoV-2 after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant.

Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as SARS-CoV-2, by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN). Herein, we demonstrate priming IM with mRNA followed by heterologous IN boosting with NE/IVT adjuvanted recombinant antigen induces strong mucosal and systemic antibody responses and enhances antigen-specific T cell responses in mucosa-draining lymph nodes compared to IM/IM and IN/IN prime/boost regimens. While all regimens induced cross-neutralizing antibodies against divergent variants and sterilizing immunity in the lungs of challenged mice, mucosal vaccination, either as homologous prime/boost or heterologous IN boost after IM mRNA prime was required to impart sterilizing immunity in the upper respiratory tract. Our data demonstrate the benefit of hybrid regimens whereby strong immune responses primed via IM vaccination are rerouted by IN vaccination to mucosal sites to provide optimal protection to SARS-CoV-2.

immunology↗

bioRxiv2021

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.

immunology↗