Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response.

Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidate, evaluate its immunogenicity using the hemagglutination inhibition assay, ELISA, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidate compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.

Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteins.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.

Alginate Gel Encapsulated with Enzybiotics Cocktail Is Effective against Multispecies Biofilms.

The development of new and effective antibacterials for pharmaceutical or cosmetic skin care that have a low potential for the emergence and expansion of bacterial resistance is of high demand in scientific and applied research. Great hopes are placed on alternative agents such as bactericidal peptidoglycan hydrolases, depolymerases, etc. Enzybiotic-based preparations are being studied for the treatment of various infections and, among others, can be used as topical formulations and dressings with protein-polysaccharide complexes. Here, we investigate the antibiofilm properties of a novel enzybiotic cocktail of phage endolysin LysSi3 and bacteriocin lysostaphin, formulated in the alginate gel matrix and its ability to control the opportunistic skin-colonizing bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as mixed-species biofilms. Our results propose that the application of SiL-gel affects different components of biofilm extracellular polymeric substances, disrupts the matrix, and eliminates the bacteria embedded in it. This composition is highly effective against biofilms composed of Gram-negative and Gram-positive species and does not possess significant cytotoxic effects. Our data form the basis for the development of antibacterial skin care products with a gentle but effective mode of action.

Parental anxiety and pediatric vaccine refusal in a US national sample of parents.

OBJECTIVES: Understanding vaccine hesitancy among parents is of emerging interest and of rising importance for promoting vaccine uptake to prevent pediatric illness. Here, we examine associations between pediatric vaccine refusal and parental symptoms of anxiety. METHODS: Our cross-sectional survey assessed pediatric vaccine refusal in 1699 parents in a US national sample. Participants completed a sociodemographic questionnaire, the Vaccine Hesitancy Scale, and symptoms of anxiety (GAD-7). RESULTS: The prevalence of pediatric vaccine refusal was 15.5 %. Parent symptoms of anxiety were related to vaccine refusal (OR = 1.07 [1.03, 1.10]). Mild (1.88 [1.39, 2.54], p <.001) and clinically significant (2.14 [1.39, 3.31], p <.001) symptoms of anxiety were also related to pediatric vaccine refusal. Parental anxiety was also associated with perceived risks of vaccines and reduced confidence. CONCLUSIONS: Findings highlight the need to consider parental anxiety in the development of public health interventions that address substandard pediatric vaccine uptake.

Prevalence of neurodevelopmental delays in infants with perinatal HIV infection in comparison with HIV exposure in rural South Africa.

BACKGROUND: Assessing neurodevelopmental functioning in early infancy is essential as this is a critical period for infant development. Infants born to mothers with HIV are at a greater risk of developmental delays than those born to mothers without HIV. In this study, we analyzed differences in early neurodevelopmental functioning for infants with HIV exposure versus HIV infection to inform infant screening and early intervention. METHODS: Participants were recruited from community health centers in Mpumalanga Province, South Africa. Prenatally, mothers completed baseline demographic assessment at 8 to 24-week gestation periods. Infant neurodevelopment was assessed using the Bayley Infant Neurodevelopmental Screener (BINS) 12 months postnatally. Five areas of development were assessed: cognition, receptive communication, expressive communication, fine motor ability, and gross motor ability. FINDINGS: Postnatal infant assessment using the BINS revealed that infants were at risk for neurodevelopmental delays across all domains assessed. Notably, infants exposed to HIV, regardless of HIV status, were 'at emerging risk' or 'at clear risk' for cognitive (43.5%), receptive communication (38.2%), expressive communication (53.1%), fine motor (49.9%), and gross motor delays (55.6%). Differences were noted by HIV status in the cognition domain, such that HIV-exposed infants were more likely to be at emerging or clear risk than HIV-infected infants. There was a different trend with gross motor delays, such that HIV-infected infants were at a greater risk for motor delays than HIV-exposed, uninfected infants. CONCLUSION: Screening tools for this vulnerable population provide valuable early life assessment to determine infant needs for intervention and treatment planning. Such interventions may mitigate the impact of HIV status on neurodevelopmental health generally and cognition.

Stationary and transient Soret separation in a binary mixture with a consolute critical point.

The stationary and transient Soret separation in a binary mixture with a consolute critical point is studied theoretically. The mixture is placed between two parallel plates kept at different temperatures. A polymer blend is used as a model system. Analytical solutions are constructed to describe the stationary separation in a binary mixture with variable Soret coefficient. The latter strongly depends on temperature and concentration and enhances near a consolute critical point due to reduced diffusion. As a result, a large concentration gradient is observed locally, while much smaller concentration variations are found in the rest of the layer. It is shown that complete separation can be obtained by applying a small temperature difference first, waiting for the establishment of stationary state, and then increasing this difference again. In this case, the critical temperature lies between hot and cold wall temperatures, while the mixture still remains in the one-phase region. When the initial (mean) temperature or concentration are shifted away from the near-critical values, the separation decreases. The analysis of transient behavior shows that the Soret separation occurs much faster than diffusion to the homogeneous state when the initial concentration is close to the critical one. It happens due to the decrease (increase) of the local relaxation time during the Soret (Diffusion) steps. The transient times of these steps become comparable for small temperature differences or off-critical initial concentrations. An unusual (non-exponential) separation dynamics is observed when the separation starts in the off-critical domain, and then enhances greatly when the system enters into the near-critical region. It is also found that the transient time decreases with increasing the applied temperature difference.