Virus-like particle-based multipathogen vaccine of FMD and SVA elicits balanced and broad protective efficacy in mice and pigs.

Inactivated vaccines lack the capability to serologically differentiate between infected and vaccinated animals, thereby impeding the effective eradication of pathogen. Conversely, vaccines based on virus-like particles (VLPs) emulate natural viruses in both size and antigenic structure, presenting a promising alternative to overcome these limitations. As the complexity of swine infectious diseases increases, the increase of vaccine types and doses may intensify the stress response. This exacerbation can lead to diminished productivity, failure of immunization, and elevated costs. Given the critical dynamics of co-infection and the clinically indistinguishable symptoms associated with foot-and-mouth disease virus (FMDV) and senecavirus A (SVA), there is a dire need for an efficacious intervention. To address these challenges, we developed a combined vaccine composed of three distinct VLPs, specifically designed to target SVA and FMDV serotypes O and A. Our research demonstrates that this trivalent VLP vaccine induces antigen-specific and robust serum antibody responses, comparable to those produced by the respective monovalent vaccines. Moreover, the immune sera from the combined VLP vaccine strongly neutralized FMDV type A and O, and SVA, with neutralization titers comparable to those of the individual vaccines, indicating a high level of immunogenic compatibility among the three VLP components. Importantly, the combined VLPs vaccines-immunized sera conferred efficient protection against single or mixed infections with FMDV type A and O, and SVA viruses in pigs. In contrast, individual vaccines could only protect pigs against homologous virus infections and not against heterologous challenges. This study presents a novel combined vaccines candidate against FMD and SVA, and provides new insights for the development of combination vaccines for other viral swine diseases.

Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets.

Porcine epidemic diarrhea virus (PEDV) is considered the cause for porcine epidemic diarrhea (PED) outbreaks and hefty losses in pig farming. However, no effective commercial vaccines against PEDV mutant strains are available nowadays. Here, we constructed three native-like trimeric candidate nanovaccines, i.e., spike 1 trimer (S1-Trimer), collagenase equivalent domain trimer (COE-Trimer), and receptor-binding domain trimer (RBD-Trimer) for PEDV based on Trimer-Tag technology. And evaluated its physical properties and immune efficacy. The result showed that the candidate nanovaccines were safe for mice and pregnant sows, and no animal death or miscarriage occurred in our study. S1-Trimer showed stable physical properties, high cell uptake rate and receptor affinity. In the mouse, sow and piglet models, immunization of S1-Trimer induced high-level of humoral immunity containing PEDV-specific IgG and IgA. S1-Trimer-driven mucosal IgA responses and systemic IgG responses exhibited high titers of virus neutralizing antibodies (NAbs) in vitro. S1-Trimer induced Th1-biased cellular immune responses in mice. Moreover, the piglets from the S1-Trimer and inactivated vaccine groups displayed significantly fewer microscopic lesions in the intestinal tissue, with only one and two piglets showing mild diarrhea. The viral load in feces and intestines from the S1-Trimer and inactivated vaccine groups were significantly lower than those of the PBS group. For the first time, our data demonstrated the protective efficacy of Trimer-Tag-based nanovaccines used for PEDV. The S1-Trimer developed in this study was a competitive vaccine candidate, and Trimer-Tag may be an important platform for the rapid production of safe and effective subunit vaccines in the future.

Synthesis and Application of Specific N2H4 Fluorescent Probes with AIE Effect Based on Pyrazole Structure.

Two fluorescent probes, Y1-2 were synthesized from 2-acetonaphthone, 4-acetylbiphenyl, and phenyl hydrazine by Vilsmeier-Haack reaction and Knoevenagel condensation. Their recognition efficacies for N2H4 were tested by UV-visible absorption spectroscopy and fluorescence emission spectroscopy. The recognition mechanism were studies by density-functional theory calculations, and the effect of pH on N2H4 recognition was also studied. The results showed that the probe Y1-2 has high selectivity and a low detection limit for N2H4, and the recognition of N2H4 can be accomplished at physiological pH. The probes have had obvious aggregation-induced luminescence effect, large Stokes shift, high sensitivity, and can be successfully applied to live cell imaging.

Exploring Hollow Mesoporous Silica Nanoparticles as a Nanocarrier in the Delivery of Foot-And-Mouth Disease Virus-like Particle Vaccines.

Virus-like particle (VLP) vaccine is considered to be the most promising candidate alternative to the traditional inactivated vaccine for foot-and-mouth disease (FMD). To elicit a desired immune response, hollow mesoporous silica nanoparticles (HMSNs) have been synthesized and utilized as a nanocarrier for FMD VLP vaccine delivery. The as-prepared HMSNs displayed a relatively small particle size (∼260 nm), large cavity (∼150 nm), and thin wall (∼55 nm). The inherent structural superiorities make them ideal nanocarriers for the FMD VLP vaccine, which exhibited good biocompatibility, great protein-loading capacity, high antibody-response level, and protective efficiency, even comparable to commercial adjuvant ISA 206. All the results suggested that HMSNs may be a valid nanocarrier in VLP-based vaccines.

[Evaluation of the humoral immunity in mice induced by foot-and-mouth disease virus-like particles-ZIF-8 complexes with different sizes].

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn2+ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.

Role of media coverage in a SVEIR-I epidemic model with nonlinear incidence and spatial heterogeneous environment.

In this paper, we propose a SVEIR-I epidemic model with media coverage in a spatially heterogeneous environment, and study the role of media coverage in the spread of diseases in a spatially heterogeneous environment. In a spatially heterogeneous environment, we first set up the well-posedness of the model. Then, we define the basic reproduction number $ R_0 $ of the model and establish the global dynamic threshold criteria: when $ R_0 < 1 $, disease-free steady state is globally asymptotically stable, while when $ R_0 > 1 $, the model is uniformly persistent. In addition, the existence and uniqueness of the equilibrium state of endemic diseases were obtained when $ R_0 > 1 $ in homogeneous space and heterogeneous diffusion environment. Further, by constructing appropriate Lyapunov functions, the global asymptotic stability of disease-free and positive steady states was established. Finally, through numerical simulations, it is shown that spatial heterogeneity can increase the risk of disease transmission, and can even change the threshold for disease transmission; media coverage can make people more widely understand disease information, and then reduce the effective contact rate to control the spread of disease.

Self-Assembling Nanovaccine Fused with Flagellin Enhances Protective Effect against Foot-and-Mouth Disease Virus.

Nanovaccines based on self-assembling nanoparticles (NPs) can show conformational epitopes of antigens and they have high immunogenicity. In addition, flagellin, as a biological immune enhancer, can be fused with an antigen to considerably enhance the immune effect of antigens. In improving the immunogenicity and stability of a foot-and-mouth disease virus (FMDV) antigen, novel FMDV NP antigens were prepared by covalently coupling the VP1 protein and truncated flagellin containing only N-terminus D0 and D1 (N-terminal aa 1-99, nFLiC) with self-assembling NPs (i301). The results showed that the fusion proteins VP1-i301 and VP1-i301-nFLiC can assemble into NPs with high thermal tolerance and stability, obtain high cell uptake efficiency, and upregulate marker molecules and immune-stimulating cytokines in vitro. In addition, compared with monomeric VP1 antigen, high-level cytokines were stimulated with VP1-i301 and VP1-i301-nFLiC nanovaccines in guinea pigs, to provide clinical protection against viral infection comparable to an inactivated vaccine. This study provides new insight for the development of a novel FMD vaccine.

Effectiveness of the booster dose of inactivated COVID-19 vaccine against Omicron BA.5 infection: a matched cohort study of adult close contacts.

BACKGROUND: Although COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic. METHODS: Based on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan-Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort. FINDINGS: Before matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15-180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18-39 years, but was not detected for those aged 40 years or older. INTERPRETATION: The receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage.

Distinguishing the Vaccine Effectiveness of Inactivated BBIBP-CorV Vaccine Booster Against the Susceptibility, Infectiousness, and Transmission of Omicron Stains: A Retrospective Cohort Study in Urumqi, China.

INTRODUCTION: With COVID-19 vaccination rolled out globally, increasing numbers of studies have shown that booster vaccines can enhance an individual's protection against the infection, hospitalization, and death caused by SARS-CoV-2. This study evaluated the effectiveness of COVID-19 vaccine BBIBP-CorV booster against being infected (susceptibility), infecting others (infectiousness), and spreading the disease from one to another (transmission). METHODS: This retrospective cohort study investigated the close contacts of all officially ascertained COVID-19 confirmed cases in Urumqi, China between August 1 and September 7, 2022. Eligible records were divided into four subcohorts based on the vaccination status of both the close contact and their source case: group 2-2, 2-dose contacts seeded by 2-dose source case (as the reference level); group 2-3, 3-dose contacts seeded by 2-dose source case; group 3-2, 2-dose contacts seeded by 3-dose source case; and group 3-3, 3-dose contacts seeded by 3-dose source case. In the four subcohorts, multivariate logistic regression models were used to examine the vaccine effectiveness (VE) for the BBIBP-CorV booster dose. We adjusted for potential confounding variables, including the sex and age of source cases and close contacts, the calendar week of contact history and contact settings. We evaluated the statistical uncertainty using a 95% confidence interval (CI). In addition, we conducted subgroup analyses to evaluate VE by sex. RESULTS: The sample sizes of groups 2-2, 2-3, 3-2, and 3-3 were 1184, 3773, 4723, and 27,136 individuals, respectively. Overall VE against susceptibility (group 2-3 vs 2-2) was 42.1% (95% CI 10.6, 62.5), VE against infectiousness (group 3-2 vs 2-2) was 62.0% (95% CI 37.2, 77.0), and VE against transmission (group 3-3 vs 2-2) was 83.7% (95% CI 75.1, 89.4). In the sex-stratified subgroups, male close contacts showed similar VE compared to the overall. However, among female close contacts, while the booster dose improved VE against infectiousness and VE against susceptibility, the VEs were not significantly different from zero. CONCLUSION: BBIBP-CorV vaccine booster was associated with mild to moderate levels of protection against Omicron susceptibility, infectiousness, and transmission. Real-world assessment of protective performance of COVID-19 vaccines against the risk of Omicron strains is continuously needed, and may provide information that helps vaccination strategy.

Qualitative analysis of a reaction-diffusion SIRS epidemic model with nonlinear incidence rate and partial immunity.

In this paper, a reaction-diffusion SIRS epidemic model with nonlinear incidence rate and partial immunity in a spatially heterogeneous environment is proposed. The well-posedness of the solution is firstly established. Then the basic reproduction number R0 is defined and a threshold dynamics is obtained. That is, when R0 < 1, the disease-free steady state is locally stable, which implies that the disease is extinct, when R0 > 1, the disease is permanent, and there exists at least one positive steady state solution. Finally, the asymptotic profiles of the positive steady state solution as individuals disperse at small and large rates are investigated. Furthermore, as an application of theoretical analysis, a numerical example involving the spread of influenza is discussed. Based on the numerical simulations, we find that the increase of transmission rate and spatial heterogeneity can enhance the risk of influenza propagation, and the increase of diffusion rate, saturation incidence for susceptible and recovery rate can reduce the risk of influenza propagation. Therefore, we propose to reduce the flow of people to lower the effect of spatial heterogeneity, increase the transfer of infected individuals to hospitals in surrounding areas to increase the diffusion rate, and increase the construction of public medical resources to increase the recovery rate for controlling influenza propagation.

A stochastic dynamical model for nosocomial infections with co-circulation of sensitive and resistant bacterial strains.

Nosocomial infections (hospital-acquired) has been an important public health problem, which may make those patients with infections or involved visitors and hospital personnel at higher risk of worse clinical outcomes or infection, and then consume more healthcare resources. Taking into account the stochasticity of the death and discharge rate of patients staying in hospitals, in this paper, we propose a stochastic dynamical model describing the transmission of nosocomial pathogens among patients admitted for hospital stays. The stochastic terms of the model are incorporated to capture the randomness arising from death and discharge processes of patients. Firstly, a sufficient condition is established for the stochastic extinction of disease. It shows that introducing randomness in the model will result in lower potential of nosocomial outbreaks. Further, we establish a threshold criterion on the existence of stationary distribution and ergodicity for any positive solution of the model. Particularly, the spectral radius form of stochastic threshold value is calculated in the special case. Moreover, the numerical simulations are conducted to both validate the theoretical results and investigate the effect of prevention and control strategies on the prevalence of nosocomial infection. We show that enhancing hygiene, targeting colonized and infected patients, improving antibiotic treatment accuracy, shortening treatment periods are all crucial factors to contain nosocomial infections.

Patch model for border reopening and control to prevent new outbreaks of COVID-19.

In this paper, we propose a two-patch model with border control to investigate the effect of border control measures and local non-pharmacological interventions (NPIs) on the transmission of COVID-19. The basic reproduction number of the model is calculated, and the existence and stability of the boundary equilibria and the existence of the coexistence equilibrium of the model are obtained. Through numerical simulation, when there are no unquarantined virus carriers in the patch-2, it can be concluded that the reopening of the border with strict border control measures to allow people in patch-1 to move into patch-2 will not lead to disease outbreaks. Also, when there are unquarantined virus carriers in patch-2 (or lax border control causes people carrying the virus to flow into patch-2), the border control is more strict, and the slower the growth of number of new infectious in patch-2, but the strength of border control does not affect the final state of the disease, which is still dependent on local NPIs. Finally, when the border reopens during an outbreak of disease in patch-2, then a second outbreak will happen.

Case clustering, contact stratification, and transmission heterogeneity of SARS-CoV-2 Omicron BA.5 variants in Urumqi, China: An observational study.

Background: From August to September 2022, Urumqi, the capital of the Xinjiang Uygur Autonomous Region in China, faced its largest COVID-19 outbreak caused by the emergence of the SARS-CoV-2 Omicron BA.5.2 variants. Although the superspreading of COVID-19 played an important role in triggering large-scale outbreaks, little was known about the superspreading potential and heterogeneity in the transmission of Omicron BA.5 variants. Methods: In this retrospective observational, contact tracing study, we identified 1139 laboratory-confirmed COVID-19 cases of Omicron BA.5.2 variants, and 51 323 test-negative close contacts in Urumqi from 7 August to 7 September 2022. By using detailed contact tracing information and exposure history of linked case-contact pairs, we described stratification in contact and heterogeneity in transmission across different demographic strata, vaccine statuses, and contact settings. We adopted beta-binomial models to characterise the secondary attack rate (SAR) distribution among close contacts and modelled COVID-19 transmission as a branching process with heterogeneity in transmission governed by negative binomial models. Results: After the city lockdown, the mean case cluster size decreased from 2.0 (before lockdown) to 1.6, with decreased proportions of contacts in workplace and community settings compared with household settings. We estimated that 14% of the most infectious index cases generated 80% transmission, whereas transmission in the community setting presented the highest heterogeneity, with 5% index cases seeding 80% transmission. Compared with zero, one, and two doses of inactivated vaccine (Sinopharm), index cases with three doses of vaccine had a lower risk of generating secondary cases in terms of the reproduction number. Contacts of female cases, cases with ages 0-17 years, and household settings had relatively higher SAR. Conclusions: In the context of intensive control measures, active case detection, and relatively high vaccine coverage, but with an infection-naive population, our findings suggested high heterogeneity in the contact and transmission risks of Omicron BA.5 variants across different demographic strata, vaccine statuses, and contact settings. Given the rapid evolution of SARS-CoV-2, investigating the distribution of transmission not only helped promote public awareness and preparedness among high-risk groups, but also highlighted the importance of continuously monitoring the transmission characteristics of genetic variants of SARS-CoV-2.

Spatial dynamics of a viral infection model with immune response and nonlinear incidence.

Incorporating humoral immunity, cell-to-cell transmission and degenerated diffusion into a virus infection model, we investigate a viral dynamics model in heterogenous environments. The model is assumed that the uninfected and infected cells do not diffuse and the virus and B cells have diffusion. Firstly, the well-posedness of the model is discussed. And then, we calculated the reproduction number R0 account for virus infection, and some useful properties of R0 are obtained by means of the Kuratowski measure of noncompactness and the principle eigenvalue. Further, when R0<1, the infection-free steady state is proved to be globally asymptotically stable. Moreover, to discuss the antibody response reproduction number R~0 of the model and the global dynamics of virus infection, including the global stability infection steady state and the uniform persistence of infection, and to obtain the k-contraction of the model with the Kuratowski measure of noncompactness, a special case of the model is considered. At the same time, when R0>1 and R~0<1 (R~0>1), we obtained a sufficient condition on the global asymptotic stability of the antibody-free infection steady state (the uniform persistence and global asymptotic stability of infection with antibody response). Finally, the numerical examples are presented to illustrate the theoretical results and verify the conjectures.

Analysis and simulation of a stochastic COVID-19 model with large-scale nucleic acid detection and isolation measures: A case study of the outbreak in Urumqi, China in August 2022.

In this paper, a stochastic COVID-19 model with large-scale nucleic acid detection and isolation measures is proposed. Firstly, the existence and uniqueness of the global positive solution is obtained. Secondly, threshold criteria for the stochastic extinction and persistence in the mean with probability one are established. Moreover, a sufficient condition for the existence of unique ergodic stationary distribution for any positive solution is also established. Finally, numerical simulations are carried out in combination with real COVID-19 data from Urumqi, China and the theoretical results are verified.

Dynamical behavior of a coupling SEIR epidemic model with transmission in body and vitro, incubation and environmental effects.

In this paper, a coupling SEIR epidemic model is proposed to characterize the interaction of virus spread in the body of hosts and between hosts with environmentally-driven infection, humoral immunity and incubation of disease. The threshold criteria on the local (or global) stability of feasible equilibria with or without antibody response are established. The basic reproduction number $ R_{b0} $ is obtained for the SEIR model without an antibody response, by which we find that the disease-free equilibrium is locally asymptotically stable if $ R_{b0} < 1 $. Two endemic equilibria exist if $ R_{b0} < 1 $, in which one is locally asymptotically stable under some additional conditions but the other is unstable, which means there is backward bifurcation. In addition, the uniform persistence of this model is discussed. For the SEIR model with an antibody response, the basic reproduction number $ R_{0} $ is calculated, from which the disease-free equilibrium is globally asymptotically stable if $ R_0\leq1 $, and the unique endemic equilibrium is globally asymptotically stable if $ R_0 > 1 $. Antibody immunity in the host plays a great role in the control of disease transmission, especially when the diseases between the hosts are entirely extinct once antibody cells in the host reach a proper level. Finally, the main conclusions are illustrated by some special examples and numerical simulations.

Poly(I:C) and CpG improve the assembly of foot-and-mouth disease virus-like particles and immune response in mice.

Virus-like particles (VLPs) are extremely potent, safe, and serviceable vaccine platforms. Good assembly efficiency of VLPs is the key to reducing vaccine production costs and eliciting a robust immune response. This study adopted CpG and Poly (I:C) as scaffolds to facilitate the assembly of foot-and-mouth disease virus (FMDV) VLPs in vitro. The VLPs and the co-assembly products were characterized by particle size, zeta potential, gel retardation measurement, nuclease digestion experiments, size-exclusion chromatography, transmission electron microscopy and circular dichroism analysis. Our results indicated the successful encapsulation of CpG and Poly (I:C) inside VLPs without any effect on shape or size. Vaccination in mice also elicited a robust immune response. This study demonstrated that CpG and Poly (I:C) improved the efficiency of FMDV VLPs assembly and enhanced immune response, further proposing a new idea for improving the efficiency of VLPs assembly and enriching the in vitro VLPs assembly strategies.

Optimal control strategy analysis for an human-animal brucellosis infection model with multiple delays.

Firstly, we consider an animal-human infection model of brucellosis with three distributed delays, representing the latent period of brucellosis in infected animal and human population and the survival time of brucella in the environment, respectively. The equilibrium points and basic reproduction number R 0 are calculated. By building appropriate Lyapunov functionals and applying LaSalle's invariance principle, the sufficient conditions for global asymptotic stability of two equilibria are given. Secondly, by introducing four control variables, we set the corresponding optimal control model and drive the first order necessary conditions for the existence of optimal control solution. Finally, we perform several numerical simulations to validate our theoretical results and show effects of different control strategies.

Development and Efficacy Evaluation of a Novel Nano-Emulsion Adjuvant for a Foot-and-Mouth Disease Virus-like Particles Vaccine Based on Squalane.

The successful development of foot-and-mouth disease virus-like particles (FMD-VLPs) has opened a new direction for researching a novel subunit vaccine for foot-and-mouth disease (FMD). Therefore, it is urgent to develop an adjuvant that is highly effective and safe to facilitate a better immune response to be pair with the FMD-VLP vaccine. In this research, we prepared a new nano-emulsion adjuvant based on squalane (SNA) containing CpG using the pseudo-ternary phase diagram method and the phase transformation method. The SNA consisted of Span85, Tween60, squalane, polyethene glycol-400 (PEG400) and CpG aqueous solution. The average particle diameter of the SNA was about 95 nm, and it exhibited good resistance to centrifugation, thermal stability, and biocompatibility. Then, SNA was emulsified as an adjuvant to prepare foot-and-mouth disease virus-like particles vaccine, BALB/c mice and guinea pigs were immunized, and we evaluated the immunization effect. The immunization results in mice showed that the SNA-VLPs vaccine significantly increased specific antibody levels in mice within 4 weeks, including higher levels of IgG1 and IgG2a. In addition, it increased the levels of IFN-γ and IL-1ß in the immune serum of mice. Meanwhile, guinea pig-specific and neutralizing antibodies were considerably increased within 4 weeks when SNA was used as an adjuvant, thereby facilitating the proliferation of splenic lymphocytes. More importantly, in guinea pigs immunized with one dose of SNA-VLPs, challenged with FMDV 28 days after immunization, the protection rate can reach 83.3%, which is as high as in the ISA-206 control group. In conclusion, the novel squalane nano-emulsion adjuvant is an effective adjuvant for the FMD-VLPs vaccine, indicating a promising adjuvant for the future development of a novel FMD-VLPs vaccine.

Dynamics in a disease transmission model coupled virus infection in host with incubation delay and environmental effects.

In this paper, a disease transmission model coupled virus infection in host with incubation delay and environmental effects is studied. For the virus infection model in host with immune, latent delay and environmental virus invading, the threshold criteria on the global stability of antibody-free and antibody response infection equilibria are established. For the disease transmission model with incubation delay and immune response in host, basic reproduction number R 0 is defined, and the local stability of equilibria are established, i.e., the disease-free equilibrium is locally asymptotically stable if R 0 < 1 , and the endemic equilibrium is locally asymptotically stable if R 0 > 1 . Furthermore, the uniform persistence of positive solutions is studied while there is not the direct transmission of disease by the infected individuals. Finally, the numerical examples are presented to verify the main results.