Parenteral Vaccination Research Articles

Supplementation of Foals with a Saccharomyces cerevisiae Fermentation Product Alters the Early Response to Vaccination.

Feed supplements supporting animal welfare and performance are becoming increasingly important. Immunomodulatory effects of such products have been observed in many species. The aim of this study was to analyze whether food supplementation with a Saccharomyces cerevisiae fermentation product (SCFP) affects the occurrence of foal diarrhea in early life, and whether the SCFP feeding has an impact on the immediate response to a parenteral vaccination at the age of 6-9 months. Eleven foals received the SCFP (OLI) and eleven foals were fed a placebo (PLA) for 29 days. Growth, diarrhea, and diarrhea severity were observed until day 30. After weaning, at the age of 6-9 months, foals were vaccinated parenterally against influenza and tetanus. The supplementation had no statistically significant effect on diarrhea duration and severity. On the day of vaccination, PLA and OLI foals did not differ significantly regarding numbers of circulating blood leukocyte subsets. However, the response to vaccination differed significantly between OLI and PLA foals. In OLI foals, the numbers of the major leukocyte fractions (granulocytes, lymphocytes, monocytes, CD4+ T cells, CD8+ T cells, CD21+ B cells, and MHC-II+/CD21- cells) increased significantly 24 h after vaccination but remained unchanged in PLA foals. The observed results suggest that early life supplementation with an SCFP may affect the early immune response to an initial vaccination.

Intranasal booster vaccination of beef steers reduces clinical signs following experimental coinfection with BRSV and BHV-1 without reducing shedding of BRD-associated bacteria.

To determine the efficacy of primary or booster intranasal vaccination of beef steers on clinical protection and pathogen detection following simultaneous challenge with bovine respiratory syncytial virus and bovine herpes virus 1. 30 beef steers were randomly allocated to 3 different treatment groups starting at 2 months of age. Group A (n = 10) was administered a single dose of a parenteral modified-live vaccine and was moved to a separate pasture. Groups B (n = 10) and C (10) remained unvaccinated. At 6 months of age, all steers were weaned and transported. Subsequently, groups A and B received a single dose of an intranasal modified-live vaccine vaccine while group C remained unvaccinated. Group C was housed separately until challenge. Two days following vaccination, all steers were challenged with bovine respiratory syncytial virus and bovine herpes virus 1 and housed in a single pen. Clinical and antibody response outcomes and the presence of nasal pathogens were evaluated. The odds of clinical disease were lower in group A compared with group C on day 7 postchallenge; however, antibody responses and pathogen detection were not significantly different between groups before and following viral challenge. All calves remained negative for Histophilus somni and Mycoplasma bovis; however, significantly greater loads of Mannheimia haemolytica and Pasteurella multocida were detected on day 7 postchallenge compared with day -2 prechallenge. Intranasal booster vaccination of beef steers at 6 months of age reduced clinical disease early after viral challenge. Weaning, transport, and viral infection promoted increased detection rates of M haemolytica and P multocida regardless of vaccination status.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

A pilot study on the impact of parenteral vaccination of free-roaming dogs within the rabies control framework in Ukraine

This pioneering study is prompted by the imperative to enhance our understanding of a constituent within Ukraine's rabies control strategy, specifically focusing on the vaccination of free-roaming canines against rabies with a local vaccine in certain endemic rabies areas. The cross-sectional study encompassed the capture, sterilization, deworming, and rabies vaccination processes in 160 free-roaming dogs, followed by the collection of blood samples to examine RABV-specific neutralising antibodies in 16 dogs (10% of the vaccinated population), captured from sectors (territories) with a higher density of population and with higher density of previously vaccinated free-roaming dogs. Half of the targeted samples comprised males (n = 8), while the remaining half consisted of females (n = 8). The median of virus-neutralising antibody level was 0.58 IU/mL, with a minimum protective threshold of 0.5 IU/mL. Antibody titers below the 0.5 IU/mL threshold were detected in 25.0% (2/8) of the male group, and in 62.5% (5/8) of the female group. Notably, male dogs exhibited a higher median antibody level of 0.66 IU/mL, compared to females, who presented a median level of 0.26 IU/mL. However, no statistically significant difference was found between the male and female groups (P = 0.36). In general, more than half of the tested population (56.3%) exceeded the 0.5 IU/mL protective threshold 4 months post-vaccination. The inadequate levels of antibodies neutralizing the rabies virus are likely a result of a confluence of factors, including stressors such as nutritional and temperature-related challenges, along with variations in the responses of individual immune systems. Considering the endemic rabies situation and large population of free-roaming dogs in Ukraine, we suggest repeated vaccination for free-roaming dogs against rabies one year after the previous vaccination. In perspective, we suggest conducting large-scale epidemiological studies to assess the impact of animal-related, vaccine-related, and environment-related parameters on the efficacy of rabies vaccines used in Ukraine.

Effects of parenteral or intranasal modified-live virus respiratory vaccination and revaccination on day 14 in auction-derived feedlot heifers

Auction-derived beef heifers were received in 12 arrival blocks and randomized to 4 treatment groups: 1) parenteral MLV vacci­nation on d 0 (INJ), 2) intranasal MLV vaccination on d 0 (INT), 3) parenteral MLV vaccination on d 0 and revaccination with intranasal on d 14 (INJ-R), 4) intranasal MLV vaccination on d 0 and revaccination with intranasal on d 14 (INT-R). Pen was experimental unit, with 12 pens/treatment and 65 to 76 heif­ers/pen in a randomized complete block design. Performance, health, carcass traits and BRSV and H. somni frequency of car­riage in the nasopharynx of revaccinated groups on d 0 and 60 was determined. Morbidity (P = 0.95), mortal­ity (P = 0.80), and other health variables (P > 0.74) did not dif­fer. However, an improvement in gain-to-feed (G:F) (P = 0.04), increased ribeye area (REA) (P ≤ 0.01) and percentage of edible livers (P ≤ 0.01) was observed for INJ and INJ-R. The BRSV (P = 0.09) and H. somni (P < 0.01) frequency of carriage in the naso­pharynx increased with time but no treatment effect (P ≥ 0.23) nor treatment x day interaction (P ≥ 0.29) existed. Revaccina­tion with an intranasal MLV did not impact health or growth, and arrival intranasal vaccination (INT and INT-R) resulted in less G:F and REA concomitant with increased liver absces­sation, compared to parenteral (INJ and INJ-R). Detection of H. somni in the nasopharynx was frequent on d 60, suggesting important prevalence of this bacterial pathogen in the south­ern U.S. cattle population.

Intranasal vaccine for Lyme disease provides protection against tick transmitted Borrelia burgdorferi beyond one year

Strategies for disease control are necessary to reduce incidence of Lyme Disease (LD) including development of safe vaccines for human use. Parainfluenza virus 5 (PIV5) vector has an excellent safety record in animals and PIV5-vectored vaccines are currently under clinical development. We constructed PIV5-vectored LD vaccine candidates expressing OspA from B. burgdorferi (OspAB31) and a chimeric protein containing sequences from B. burgdorferi and B. afzelii (OspABPBPk). Immunogenicity and vaccine efficacy were analyzed in C3H-HeN mice after prime-boost intranasal vaccination with live PIV5-OspAB31 or PIV5-OspABPBPk, subcutaneous (s.c.) vaccination with rOspAB31+Alum, and the respective controls. Mice vaccinated intranasally with live PIV5-AB31 or PIV5-ABPBPk had higher endpoint titers of serum antibody against OspAB31 at 6- and 12- months post vaccination, compared to mice vaccinated s.c. with rOspAB31. Neutralization activity of antibody was maintained up to 18-months post-immunization, with the response greater in live PIV5-delivered OspA vaccines, than that induced by s.c. rOspAB31. Challenge with infected ticks carrying 10-19 strains of B. burgdorferi performed at 4-, 9- or 15-months post-immunization showed increased breakthrough infections in mice vaccinated with s.c. rOspAB31 compared to intranasal PIV5-AB31 or PIV5-ABPBPk at 9- and 15-months, as determined by quantification of serologic antibodies to B. burgdorferi proteins as well as flaB DNA in tissues, and by visualization of motile B. burgdorferi in culture of tissues under dark field microscope. These findings indicate that immunization of mice with PIV5 delivered OspA generates immune responses that produce longer-lasting protection ( > 1 year) against tick-transmitted B. burgdorferi than a parenteral recombinant OspA vaccine.

MRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents

Despite the availability of live-attenuated oral vaccines, rotavirus remains a major cause of severe childhood diarrhea worldwide. Due to the growing demand for parenteral rotavirus vaccines, we developed mRNA-based vaccine candidates targeting the viral spike protein VP8*. Our monomeric P2 (universal T cell epitope)-VP8* mRNA design is equivalent to a protein vaccine currently in clinical development, while LS (lumazine synthase)-P2-VP8* was designed to form nanoparticles. Cyro-electron microscopy and western blotting-based data presented here suggest that proteins derived from LS-P2-VP8* mRNA are secreted in vitro and self-assemble into 60-mer nanoparticles displaying VP8*. mRNA encoded VP8* was immunogenic in rodents and introduced both humoral and cellular responses. LS-P2-VP8* induced superior humoral responses to P2-VP8* in guinea pigs, both as monovalent and trivalent vaccines, with encouraging responses detected against the most prevalent P genotypes. Overall, our data provide evidence that trivalent LS-P2-VP8* represents a promising mRNA-based next-generation rotavirus vaccine candidate.

Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV

Although mRNA SARS-CoV-2 vaccines are generally safe and effective, in certain immunocompromised individuals they can elicit poor immunogenic responses. Among these individuals, people living with HIV (PLWH) have poor immunogenicity to several oral and parenteral vaccines. As the gut microbiome is known to affect vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immune responses to the BNT162b2 mRNA SARS-CoV-2 vaccine in healthy controls and PLWH after two doses of BNT162b2. Individuals with high spike IgG titers and high spike-specific CD4+ T-cell responses against SARS-CoV-2 showed low α-diversity in the gut. Here, we investigated and presented initial evidence that the gut microbial composition influences the response to BNT162b2 in PLWH. From our predictive models, Bifidobacterium and Faecalibacterium appeared to be microbial markers of individuals with higher spike IgG titers, while Cloacibacillus was associated with low spike IgG titers. We therefore propose that microbiome modulation could optimize immunogenicity of SARS-CoV-2 mRNA vaccines.

Diversification of a Novel α-Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines.

The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α-galactosyl ceramide (α-GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B-cell activation. Herein, we introduce a novel derivatization hotspot at the α-GalCer skeleton, namely the N-substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self-adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen-specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α-GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α-GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.

Diversification of a Novel α‐Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines

AbstractThe development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α‐galactosyl ceramide (α‐GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B‐cell activation. Herein, we introduce a novel derivatization hotspot at the α‐GalCer skeleton, namely the N‐substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self‐adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen‐specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α‐GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α‐GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.

Intranasal G5-BGG/pDNA Vaccine Elicits Protective Systemic and Mucosal Immunity against SARS-CoV-2 by Transfecting Mucosal Dendritic Cells.

Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA (pSP), named G5-BGG/pSP complex, is developed to activate NALT and to promote both systemic and mucosal immune defense. G5-BGG/pSP could traverse mucosal barriers and deliver DNA to the target cells because of its superior nasal retention and permeability characteristics. The intranasal G5-BGG/pSP complex elicits robust antigen-specific immune responses, such as the notable production of IgG antibody against several virusvariants. More importantly, it induces elevated levels of antigen-specific IgA antibody and a significant expansion of the lung-resident T lymphocyte population. Notably, the intranasal G5-BGG/pSP complex results in antigen expression and maturation of dendritic cells in nasal mucosae. These findings exhibit the potential of G5-BGG, a novel cationic material, as an effective gene carrier for intranasal vaccines to obtain robust systemic and mucosal immunity.

Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach.

Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach. Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers. Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only. MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.

Effects of intranasal or parenteral respiratory vaccination administered on-arrival or delayed in auction-derived feedlot heifers

The objective was to evaluate health, performance and serum antibody responses of auction-derived heifers to an intranasal or parenteral MLV administered on d 0 or 28. Three arrival blocks of heifers, initial BW = 459 lb ± 1.7 lb (208 kg ± 27kg; n = 600), were randomly assigned to treatments consisting of 15 pens/treatment with pen as the experimental unit and 10 heifers/pen. Treatments were: 1) Bovilis® Nasalgen® 3 and Bovilis® Vista® BVD on d 0 (NAS0); 2) Bovilis® Vista® 5 SQ on d 0 (VIS0); 3) Bovilis® Nasalgen® 3 and Bovilis® Vista® BVD on d 28 (NAS28); 4) Bovilis® Vista® 5 SQ on d 28 (VIS28). Body weight and blood samples were collected on d 0, 28 and 56. Activity (351.4 vs 354.3 min/d) and rumination time (282.6 vs 285.4 min/d) was less (P < 0.01) for delayed vs arrival vaccinated heifers. A timing χ vaccine χ day interaction existed (P < 0.01) for BRSV- and IBRV-specific antibody titers; VIS28 had the greatest (P < 0.01) BRSV antibody titer on d 56. For IBRV antibody titer on d 28, VIS0 was greatest, NAS0 was intermediate, and VIS28 and NAS28 were least (P < 0.01). Percentage of chronically ill heifers were reduced for arrival vs delayed (1.3 vs 4.7%; P = 0.02) and arrival vaccinated had a reduction in antimicrobial treatment cost ($4.63 vs $7.31; P = 0.02). Data indicate improvement in some health outcomes for the parenteral route and arrival timing of MLV, but performance was not affected.

Oral mucosa immunity: ultimate strategy to stop spreading of pandemic viruses.

Global pandemics are most likely initiated via zoonotic transmission to humans in which respiratory viruses infect airways with relevance to mucosal systems. Out of the known pandemics, five were initiated by respiratory viruses including current ongoing coronavirus disease 2019 (COVID-19). Striking progress in vaccine development and therapeutics has helped ameliorate the mortality and morbidity by infectious agents. Yet, organism replication and virus spread through mucosal tissues cannot be directly controlled by parenteral vaccines. A novel mitigation strategy is needed to elicit robust mucosal protection and broadly neutralizing activities to hamper virus entry mechanisms and inhibit transmission. This review focuses on the oral mucosa, which is a critical site of viral transmission and promising target to elicit sterile immunity. In addition to reviewing historic pandemics initiated by the zoonotic respiratory RNA viruses and the oral mucosal tissues, we discuss unique features of the oral immune responses. We address barriers and new prospects related to developing novel therapeutics to elicit protective immunity at the mucosal level to ultimately control transmission.

Barriers to the Use of Recombinant Bacterial Endotoxins Test Methods in Parenteral Drug, Vaccine and Device Safety Testing.

The Bacterial Endotoxins Test (BET) is a critical safety test that is used to detect bacterial endotoxins, which are the major contributor to fever-inducing contamination risks known as pyrogens. All parenteral therapies, including every lot of injected drugs, vaccines, medical devices, must be tested for pyrogens to ensure patient safety. Bacterial endotoxins test methods were developed as a highly sensitive detection method for bacterial endotoxins, after the discovery of a clotting cascade in horseshoe crab blood. However, horseshoe crab species are limited to some inshore coastal habitats along the Atlantic coast of the USA and others throughout Asia. Fully functional horseshoe crab clotting factors can be manufactured via recombinant protein production, and several BET methods featuring recombinant horseshoe crab proteins have now been developed for commercial use. Recombinant Bacterial Endotoxins Test (rBET) methods based on the use of recombinant Factor C (rFC) were established in the European Pharmacopoeia - however, these methods have not yet been granted compendial status in the United States Pharmacopoeia (USP). In order to facilitate dialogue between stakeholders, the Physicians Committee for Responsible Medicine hosted two virtual roundtable discussions on the perceived barriers to the use of rBET methods for US FDA requirements. Stakeholders agreed that multiple rFC-based methods have been demonstrated to have suitable analytical performance, as described in ICH Q2 on the Validation of Analytical Procedures and USP <1225> on the Validation of Compendial Procedures. United States Pharmacopoeia compendial inclusion of the rFC-based and other rBET methods was favoured, in order to reduce the additional burdens created by a lack of global harmonisation on BET testing requirements.

Characterization and immunogenicity of a novel chimeric hepatitis B core-virus like particles (cVLPs) carrying rotavirus VP8*protein in mice model

Given the efficacy and safety issues of the WHO for approved/prequalified live attenuated rotavirus (RV) vaccines, studies on alternative non-replicating modals and proper RV antigens are actively undertaken. Herein, we report the novel chimeric hepatitis B core-virus like particles (VLPs) carrying RV VP8*26-231 protein of a P [8] strain (cVLPVP8*), as a parenteral VLP RV vaccine candidate. SDS-PAGE and Western blotting analyses indicated the expected size of the E. coli-derived HBc-VP8* protein that self-assembled to cVLPVP8* particles. Immunization in mice indicated development of higher levels of IgG and IgA as well as higher IgG1/IgG2a ratios by cVLPVP8* vaccination compared to the VP8* alone. Assessment of neutralizing antibodies (nAbs) indicated development of heterotypic nAbs with cross-reactivity to a heterotypic RV strain by cVLPVP8* immunization compared to VP8* alone. The observed anti-VP8* cross-reactivity might indicate the possibility of developing a Pan-genomic RVA vaccine based on the cVLPVP8* formulation that deserves further challenge studies.

Outer membrane vesicle-based intranasal vaccines.

Delivery of vaccines via the mucosal route is regarded as the most effective mode of immunization to counteract infectious diseases that enter via mucosal tissues, including oral, nasal, pulmonary, intestinal, and urogenital surfaces. Mucosal vaccines not only induce local immune effector elements, such as secretory Immunoglobulin A (IgA) reaching the luminal site of the mucosa, but also systemic immunity. Moreover, mucosal vaccines may trigger immunity in distant mucosal tissues because of the homing of primed antigen-specific immune cells towardlocal and distant mucosal tissue via the common mucosal immune system. While most licensed intramuscular vaccines induce only systemic immunity, next-generation mucosal vaccines may outperform parenteral vaccination strategies by also eliciting protective mucosal immune responses that block infection and/or transmission. Especially the nasal route of vaccination, targeting the nasal-associated lymphoid tissue, is attractive for local and distant mucosal immunization. In numerous studies, bacterial outer membrane vesicles (OMVs) have proved attractive as vaccine platform for homologous bacterial strains, but also as antigen delivery platform for heterologous antigens of nonbacterial diseases, including viruses, parasites, and cancer. Their application has also been extended to mucosal delivery. Here, we will summarize the characteristics and clinical potential of (engineered) OMVs as vaccine platform for mucosal, especially intranasal delivery.

Comparative effectiveness of intranasal and parenteral vaccines for prevention of bovine respiratory disease in feedlot heifers

Comparative effectiveness of intranasal and parenteral vaccines for prevention of bovine respiratory disease in feedlot heifers

Integrative transcriptomic and metabolomic analysis in mice reveals the mechanism by which ginseng stem-leaf saponins enhance mucosal immunity induced by a porcine epidemic diarrhea virus vaccination

Porcine epidemic diarrhea virus (PEDV) is a main cause of severe enteric disease in piglets, leading to millions of dollars lost annually in the global pig industry. Parenteral vaccination is limited in generating sufficient mucosal immunity, which is crucial for early defense against PEDV. Here, we orally administered ginseng stem-leaf saponins (GSLS) to mice before parenteral vaccination and found that GSLS significantly enhanced the phagocytosis of dendritic cells, promoted the activities of CD4+ T cells and increased PEDV-specific IgA antibodies in the intestinal mucosa. Transcriptomic results showed that the altered genes following GSLS treatment were mostly related to the immune response and metabolism. In addition, integrated analysis of the transcriptome and metabolome revealed that the mechanism by which GSLS enhances mucosal immunity may be associated with progesterone-related pathways. Further studies are needed to explore the detailed molecular mechanisms.

A nasal vaccine with inactivated whole-virion elicits protective mucosal immunity against SARS-CoV-2 in mice.

Vaccinations are ideal for reducing the severity of clinical manifestations and secondary complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, SARS-CoV-2 continues to cause morbidity and mortality worldwide. In contrast to parenteral vaccines such as messenger RNA vaccines, nasal vaccines are expected to be more effective in preventing viral infections in the upper respiratory tract, the primary locus for viral infection and transmission. In this study, we examined the prospects of an inactivated whole-virion (WV) vaccine administered intranasally against SARS-CoV-2. Mice were immunized subcutaneously (subcutaneous vaccine) or intranasally (nasal vaccine) with the inactivated WV of SARS-CoV-2 as the antigen. The spike protein (S)-specific IgA level was found to be higher upon nasal vaccination than after subcutaneous vaccination. The level of S-specific IgG in the serum was also increased by the nasal vaccine, although it was lower than that induced by the subcutaneous vaccine. The nasal vaccine exhibited a stronger defense against viral invasion in the upper respiratory tract than the subcutaneous vaccine and unimmunized control; however, both subcutaneous and nasal vaccines provided protection in the lower respiratory tract. Furthermore, we found that intranasally administered inactivated WV elicited robust production of S-specific IgA in the nasal mucosa and IgG in the blood of mice previously vaccinated with messenger RNA encoding the S protein. Overall, these results suggest that a nasal vaccine containing inactivated WV can be a highly effective means of protection against SARS-CoV-2 infection.