Vaccine Efficacy Research Articles

Study of humoral and cellular immunity following the immunization of C57Bl/6 mice with a prototype of the inactivated Chikungunya vaccine

Introduction. Chikungunya virus infection is a problem for the health care system of affected regions due to the lack of specific prevention, as well as effective antiviral drugs. The critical role of cellular immunity in viral control and clearance for the Chikungunya fever has been demonstrated in many studies. Therefore, effective stimulation of not only humoral but also cellular immunity is of undeniable importance when assessing the effectiveness of a potential vaccine for the prevention of this infection. The aim of the present study was to investigate the formation of protective immunity after administration of a drug containing inactivated Chikungunya virus (CHIKV) to C57Bl/6 mice. Materials and methods. Inactivated CHIKV (concentrations of 10 μg and 40 μg) was administered intramuscularly to C57Bl/6 mice twice with an interval of 14 days. Indicators of humoral immunity were assessed by ELISA and neutralization test (NT), cellular immunity — by the production of IFN-γ and splenocyte proliferation in vitro. The concentration of cytokines IL-1, IL-2, IL-6, IL-10, IL-12p70 and TNF was determined by ELISA. When assessing the protective immunity in animals, CHIKV was injected into the dorsal surface of the foot of the right hind paw at a dose of 2.89 ± 0.10 lg TCD50 in a volume of 20 μl. Results. The most pronounced immune response was noted to the administration of 40 μg of inactivated CHIKV, which was manifested in the balanced production of the studied cytokines, the formation of specific humoral (according to the results of ELISA and NT) and cellular — specific proliferation of splenocytes in vitro and production of IFN-γ. When assessing efficacy, the development of foot edema in immunized animals was significantly lower than in animals in the control group. Discussion. CHIKV, inactivated by beta-propiolactone, had pronounced immunogenic properties. The balance of production of pro- and anti-inflammatory cytokines, as well as the Th1/Th2 immune response, characterized the formation of adaptive immunity in mice without a pronounced inflammatory response. The formation of a specific humoral and cellular immune response has been demonstrated. A study of protection in a non-lethal animal model confirmed the efficacy of the inactivated vaccine. Conclusion. Double administration of the inactivated CHIKV vaccine at a dose of 40 μg to C57Bl/6 mice demonstrated pronounced immunogenicity, which allows us to evaluate it as a promising prophylactic vaccine.

Preventive Efficacy, Safety, Immunogenic Activity, and Evaluation of Post-Vaccination Responses Following Immunization with Combined Trivalent Vaccine Vaktrivir (Measles-Rubella-Parotitis) in Premature Infants

Background. Registration of combined trivalent vaccine Vaktrivir (measles-rubella-parotitis) in Russia necessitates studies on its preventive efficacy, safety, immunogenic activity, and post-vaccination responses following the immunization of premature infants. Objective. The aim of the study is to evaluate efficacy, safety, and immunogenic activity of combined trivalent vaccine (measles-rubella-parotitis) and level of post-vaccination responses following the immunization of premature infants. Methods. Experimental studies were conducted to evaluate safety, immunogenicity, and postvaccinal responses after immunization of premature infants with combined within prospective comparative clinical observation. Results. Administration of the combined trivalent vaccine Vaktrivir (measles-rubella-parotitis) in premature infants has shown: no cases of measles, rubella or parotitis among vaccinated persons within prospective clinical observation for 2 years; no disturbances in parameters of clinical blood analysis, biochemical blood count, total IgE, IgA, IgM, IgG (immunogram), or urine analysis among vaccinated children over time; no subjective perceptions, adverse events signs at physical examination among vaccinated compared to baseline parameters; low post-vaccination reactions (6.7%) and similar tolerance of trivalent vaccine Vaktrivir among full-term infants (3.3%) (p = 0.301). Conclusion. Administration of the combined trivalent vaccine Vaktrivir (measles-rubella-parotitis) in premature infants has demonstrated high safety profile and immunogenic properties for measles, rubella and parotitis components, good tolerability, and low post-vaccination responses after immunization, comparable to vaccination of full-term infants.

Leukocyte dynamics in vaccinated and unvaccinated animals following dual challenge with Bovine Viral Diarrhea Virus-Mannheimia haemolytica model to compare vaccine efficacy in calves

Bovine respiratory disease continues to be the greatest threat to calf health. One of the common recommendations is to vaccinate young beef and dairy calves at 30-60 days of age to provide protection at weaning or when commingled. The study objective was to determine whether there were any dif­ferential leukocyte changes that could be measured following a dual challenge with Bovine Viral Diarrhea Virus (BVDV) and M. haemolytica ~5 months after vaccination.

Decoding bovine coronavirus immune targets: an epitope informatics approach

Bovine coronavirus (BCoV) poses a significant threat to the global cattle industry, causing both respiratory and gastrointestinal infections in cattle populations. This necessitates the development of efficacious vaccines. While several inactivated and live BCoV vaccines exist, they are predominantly limited to calves. The immunization of adult cattle is imperative for BCoV infection control, as it curtails viral transmission to calves and ameliorates the impact of enteric and respiratory ailments across all age groups within the herd. This study presents an in silico methodology for devising a multiepitope vaccine targeting BCoV. The spike glycoprotein (S) and nucleocapsid (N) proteins, which are integral elements of the BCoV structure, play pivotal roles in the viral infection cycle and immune response. We constructed a remarkably effective multiepitope vaccine candidate specifically designed to combat the BCoV population. Using immunoinformatics technology, B-cell and T-cell epitopes were predicted and linked together using linkers and adjuvants to efficiently trigger both cellular and humoral immune responses in cattle. The in silico construct was characterized, and assessment of its physicochemical properties revealed the formation of a stable vaccine construct. After 3D modeling of the vaccine construct, molecular docking revealed a stable interaction with the bovine receptor bTLR4. Moreover, the viability of the vaccine’s high expression and simple purification was demonstrated by codon optimization and in silico cloning expression into the pET28a (+) vector. By applying immunoinformatics approaches, researchers aim to better understand the immune response to bovine coronavirus, discover potential targets for intervention, and facilitate the development of diagnostic tools and vaccines to mitigate the impact of this virus on cattle health and the livestock industry. We anticipate that the design will be useful as a preventive treatment for BCoV sickness in cattle, opening the door for further laboratory studies.

Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice

H7N9 subtype avian influenza virus (AIV) poses a great challenge to poultry industry. Virus-like particle (VLP) is a prospective alternative for the traditional egg-based influenza vaccines. N-linked glycosylation (NLG) regulates the efficacy of influenza vaccines, whereas the impact of NLG modifications on the efficacy of influenza VLP vaccines remains unclear. Here, H7N9 VLPs were assembled in insect cells through co-infection with the baculoviruses expressing the NLG-modified hemagglutinin (HA), neuraminidase and matrix proteins, and the VLP vaccines were assessed in chickens and mice. NLG modifications significantly enhanced hemagglutination-inhibition and virus neutralization antibody responses in mice, rather than in chickens, because different immunization strategies were used in these animal models. The presence of dual NLG at residues 133 and 158 significantly elevated HA-binding IgG titers in chickens and mice. The VLP vaccines conferred complete protection and significantly suppressed virus replication and lung pathology post challenge with H7N9 viruses in chickens and mice. VLP immunization activated T cell immunity-related cytokine response and inhibited inflammatory cytokine response in mouse lung. Of note, the presence of dual NLG at residues 133 and 158 optimized the capacity of the VLP vaccine to stimulate interleukin-4 expression, inhibit virus shedding or alleviate lung pathology in chickens or mice. Intriguingly, the VLP vaccine with NLG addition at residue 133 provided partial cross-protection against the H5Nx subtype AIVs in chickens and mice. In conclusion, dual NLG at residues 133 and 158 in HA can be potentially used to enhance the efficacy of H7N9 VLP vaccines in chickens and mammals.

Targeting gut microbiota for immunotherapy of diseases

Targeting gut microbiota for immunotherapy of diseases

Comparative Analysis of Vaccine-Induced Neutralizing Antibodies against the Alpha, Beta, Delta, and Omicron Variants of SARS-CoV-2

The SARS-CoV-2 virus has infected more than 660 million people and caused nearly seven million deaths worldwide. During the pandemic, a number of SARS-CoV-2 vaccines were rapidly developed, and several are currently licensed for use in Europe. However, the optimization of vaccination regimens is still ongoing, particularly with regard to booster vaccinations. At the same time, the emergence of new virus variants poses an ongoing challenge to vaccine efficacy. In this study, we focused on a comparative analysis of the neutralization capacity of vaccine-induced antibodies against four different variants of concern (i.e., Alpha, Beta, Delta, and Omicron) after two and three doses of COVID-19 vaccine. We were able to show that both two (prime/boost) and three (prime/boost/boost) vaccinations elicit highly variable levels of neutralizing antibodies. In addition, we did not observe a significant difference in antibody levels after two and three vaccinations. We also observed a significant decrease in the neutralization susceptibility of all but one SARS-CoV-2 variants to vaccine-induced antibodies. In contrast, a SARS-CoV-2 breakthrough infection between the second and third vaccination results in overall higher levels of neutralizing antibodies with a concomitant improved neutralization of all virus variants. Titer levels remained highly variable across the cohort but a common trend was observed. This may be due to the fact that at the time of this study, all licensed vaccines were still based exclusively on wild-type SARS-CoV-2, whereas infections were caused by virus variants. Overall, our data demonstrate the importance of (booster) vaccinations, but at the same time emphasize the need for the continued adaptation of vaccines to induce a protective immune response against virus variants in order to be prepared for future (seasonal) SARS-CoV-2 outbreaks.

Exosome-like Systems: From Therapies to Vaccination for Cancer Treatment and Prevention—Exploring the State of the Art

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although significant progress has been made in this field, innovative approaches are needed to reduce tumor incidence, progression, and spread. In particular, the development of cancer vaccines is currently ongoing as both a preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayer vesicles that carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce direct or indirect stimulation of the immune system. In particular, EX-based vaccines may cause an anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibiting disease development. This review delves into EX composition, biogenesis, and immune-modulating properties, exploring their role as a tool for prevention and therapy in solid tumors. Finally, we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Identification of equine mares as reservoir hosts for pathogenic species of Leptospira

Equine leptospirosis can result in abortion, stillbirth, neonatal death, placentitis, and uveitis. Horses can also act as subclinical reservoir hosts of infection, which are characterized as asymptomatic carriers that persistently excrete leptospires and transmit disease. In this study, PCR and culture were used to assess urinary shedding of pathogenic Leptospira from 37 asymptomatic mares. Three asymptomatic mares, designated as H2, H8, and H9, were PCR-positive for lipL32, a gene specific for pathogenic species of Leptospira. One asymptomatic mare, H9, was culture-positive, and the recovered isolate was classified as L. kirschneri serogroup Australis serovar Rushan. DNA capture and enrichment of Leptospira genomic DNA from PCR-positive, culture-negative samples determined that asymptomatic mare H8 was also shedding L. kirschneri serogroup Australis, whereas asymptomatic mare H2 was shedding L. interrogans serogroup Icterohaemorrhagiae. Sera from all asymptomatic mares were tested by the microscopic agglutination test (MAT) and 35 of 37 (94.6%) were seropositive with titers ranging from 1:100 to 1:3200. In contrast to asymptomatic mares, mare H44 presented with acute spontaneous abortion and a serum MAT titer of 1:102,400 to L. interrogans serogroup Pomona serovar Pomona. Comparison of L. kirschneri serogroup Australis strain H9 with that of L. interrogans serogroup Pomona strain H44 in the hamster model of leptospirosis corroborated differences in virulence of strains. Since lipopolysaccharide (LPS) is a protective antigen in bacterin vaccines, the LPS of strain H9 (associated with subclinical carriage) was compared with strain H44 (associated with spontaneous abortion). This revealed different LPS profiles and immunoreactivity with reference antisera. It is essential to know what species and serovars of Leptospira are circulating in equine populations to design efficacious vaccines and diagnostic tests. Our results demonstrate that horses in the US can act as reservoir hosts of leptospirosis and shed diverse pathogenic Leptospira species via urine. This report also details the detection of L. kirschneri serogroup Australis serovar Rushan, a species and serotype of Leptospira, not previously reported in the US.

Construction of lymph nodes-targeting tumor vaccines by using the principle of DNA base complementary pairing to enhance anti-tumor cellular immune response

Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.Graphical

A Chymotrypsin-Dependent Live-Attenuated Influenza Vaccine Provides Protective Immunity against Homologous and Heterologous Viruses

Influenza virus is one of the main pathogens causing respiratory diseases in humans. Vaccines are the most effective ways to prevent viral diseases. However, the limited protective efficacy of current influenza vaccines highlights the importance of novel, safe, and effective universal influenza vaccines. With the progress of the COVID-19 pandemic, live-attenuated vaccines delivered through respiratory mucosa have shown robustly protective efficacy. How to obtain a safe and effective live-attenuated vaccine has become a major challenge. Herein, using the influenza virus as a model, we have established a strategy to quickly obtain a live-attenuated vaccine by mutating the cleavage site of the influenza virus. This mutated influenza virus can be specifically cleaved by chymotrypsin. It has similar biological characteristics to the original strain in vitro, but the safety is improved by at least 100 times in mice. It can effectively protect against lethal doses of both homologous H1N1 and heterologous H5N1 viruses post mucosal administration, confirming that the vaccine generated by this strategy has good safety and broad-spectrum protective activities. Therefore, this study can provide valuable insights for the development of attenuated vaccines for respiratory viruses or other viruses with cleavage sites.

Geospatial mapping of public sentiment and infodemic on human papillomavirus vaccination in India: An indication to formulation of strategies for effective implementation

ABSTRACT The implementation of Human Papillomavirus (HPV) vaccination is crucial for eliminating cervical cancer in India. The infodemic, characterised by misleading information, could hinder the successful implementation of the initiative. Misinformation related to the HPV vaccine, such as rumours, has been reported and circulated, contributing to an alarming pattern of vaccine hesitancy observed on social media. This study aimed to identify the public sentiment towards HPV vaccination based on the ‘Behavioral and Social Drivers (BeSD)’ framework through geospatial, content and sentiment analysis. A total of 1,487 tweets were extracted. After preprocessing, 1010 tweets were identified for sentiment and content analysis. The sentiments expressed towards the HPV vaccine are mixed, with a generally positive outlook on the vaccines. Within the population, there is a pervasive proliferation of misinformation, primarily focusing on vaccine safety and efficacy, contentious subjects, ethical considerations, and a prevalent sense of uncertainty in selecting the appropriate vaccine. These observations are crucial for developing targeted strategies to address public concerns and enhance vaccination rates. The insights gained from these results will guide policymakers, healthcare practitioners, and public health organisations to implement evidence-based interventions, thereby countering vaccine hesitancy and improving public health outcomes.

Bergenin potentiates BCG efficacy by enriching mycobacteria-specific adaptive memory responses via the Akt-Foxo-Stat4 axis

The extensive inability of the BCG vaccine to produce long-term immune protection has not only accelerated the disease burden but also progressed towards the onset of drug resistance. In our previous study, we have reported the promising effects of Bergenin (Berg) in imparting significant protection as an adjunct immunomodulator against tuberculosis (TB). In congruence with our investigations, we delineated the impact of Berg on T cells, wherein it enhanced adaptive memory responses by modulating key transcription factors, STAT4 and Akt. We translated this finding into the vaccine model of TB and observed a notable reduction in the burden of Mycobacterium tuberculosis (M.tb) in BCG-Berg co-immunized mice as compared to BCG vaccination. Moreover, Berg, along with BCG, also aided in a heightened proinflammatory response milieu that corroborates the host protective immune response against TB. Furthermore, this response aligns with the escalated central and resident memory responses by modulating the Akt-Foxo-Stat4 axis, which plays a crucial role in enhancing the vaccine efficacy of BCG. These findings showcase the utilization of immunomodulator Berg as an immunoprophylactic agent to upgrade immunological memory, making it a more effective defender against TB.

Antibody Response against SARS-CoV-2 after mRNA Vaccine in a Cohort of Hospital Healthy Workers Followed for 17 Months

The assessment of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to verify the protective efficacy of available vaccines. Hospital healthcare workers play an essential role in the care and treatment of patients and were particularly at risk of contracting the SARS-CoV-2 infection during the pandemic. The vaccination protocol introduced in our hospital protected the workers and contributed to the containment of the infection’ s spread and transmission, although a reduction in vaccine efficacy against symptomatic and breakthrough infections in vaccinated individuals was observed over time. Here, we present the results of a longitudinal and prospective analysis of the anti-SARS-CoV-2 antibodies at multiple time points over a 17-month period to determine how circulating antibody levels change over time following natural infection and vaccination for SARS-CoV-2 before (T0–T4) and after the spread of the omicron variant (T5–T6), analyzing the antibody response of 232 healthy workers at the Pio XI hospital in Desio. A General Estimating Equation model indicated a significant association of the antibody response with time intervals and hospital area, independent of age and sex. Specifically, a similar pattern of antibody response was observed between the surgery and administrative departments, and a different pattern with higher peaks of average antibody response was observed in the emergency and medical departments. Furthermore, using a logistic model, we found no differences in contracting SARS-CoV-2 after the third dose based on the hospital department. Finally, analysis of antibody distribution following the spread of the omicron variant, subdividing the cohort of positive individuals into centiles, highlighted a cut-off of 550 BAU/mL and showed that subjects with antibodies below this are more susceptible to infection than those with a concentration above the established cut-off value.

Long-term stability and immunogenicity of lipid nanoparticle COVID-19 mRNA vaccine is affected by particle size

ABSTRACT Messenger ribonucleic acid (mRNA) technology has been rapidly applied for the development of the COVID-19 vaccine. However, naked mRNA itself is inherently unstable. Lipid nanoparticles (LNPs) protect mRNAs from extracellular ribonucleases and facilitate mRNA trafficking. For mRNA vaccines, antigen-presenting cells utilize LNPs through uptake to elicit antigen-specific immunity. There are reports on the impact of various physical characteristics of LNPs, particularly those with sizes less than 200 nm, especially 50 to 150 nm, on the overall stability and protective efficacy of mRNA vaccines. To address this, a single change in the size of LNPs using the same mRNA stock solution was assessed for the physicochemical characterization of the resulting mRNA-LNPs vaccine, along with the evaluation of their protective efficacy. Particles of smaller sizes generally disperse more effectively in solutions, with minimized occurrence of particle precipitation and aggregation. Here, we demonstrate that the vaccine containing 80–100 nm mRNA-LNPs showed the best stability and protection at 4°C and −20°C. Furthermore, we can conclude that freezing the vaccine at −20°C is more appropriate for maintaining stability over the long term. This effort is poised to provide a scientific basis for improving the quality of ongoing mRNA vaccine endeavors and providing information on the development of novel products.

Genotypic analysis of RTS,S/AS01E malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.

The first licensed malaria vaccine, RTS,S/AS01E, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy. Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01E regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291. We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01E regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01E regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053). All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.

Durable lymph-node expansion is associated with the efficacy of therapeutic vaccination.

Following immunization, lymph nodes dynamically expand and contract. The mechanical and cellular changes enabling the early-stage expansion of lymph nodes have been characterized, yet the durability of such responses and their implications for adaptive immunity and vaccine efficacy are unknown. Here, by leveraging high-frequency ultrasound imaging of the lymph nodes of mice, we report more potent and persistent lymph-node expansion for animals immunized with a mesoporous silica vaccine incorporating a model antigen than for animals given bolus immunization or standard vaccine formulations such as alum, and that durable and robust lymph-node expansion was associated with vaccine efficacy and adaptive immunity for 100 days post-vaccination in a mouse model of melanoma. Immunization altered the mechanical and extracellular-matrix properties of the lymph nodes, drove antigen-dependent proliferation of immune and stromal cells, and altered the transcriptional features of dendritic cells and inflammatory monocytes. Strategies that robustly maintain lymph-node expansion may result in enhanced vaccination outcomes.

Asymptomatic parasitemia and RTS,S vaccine efficacy.

Asymptomatic parasitemia and RTS,S vaccine efficacy.

Molecular characterization and bivalent vaccine development of Aeromonas hydrophila and Aeromonas veronii in Nile tilapia (Oreochromis niloticus)

In the present study, nine strains of Aeromonas spp. were isolated from diseased Nile tilapia in Thailand and identified based on 16S rRNA and gyrB gene sequences and multilocus sequence typing (MLST) analysis. Phenotypic characterization was performed for all the isolates. For the antimicrobial susceptibility test, all isolates were resistant to amoxicillin, whereas most of the isolates were susceptible to enrofloxacin. Pathogenicity analysis revealed that most A. hydrophila strains were highly virulent to fish, corresponding with the hemolytic activity test demonstrating that clear hemolysis occurred on sheep blood agar. To develop a vaccine for fish against A. veronii and A. hydrophila infection, a bivalent vaccine based on the formalin-killed cells (FKC) of A. veronii A5 and A. hydrophila A9, which showed higher virulence to fish, was prepared. This FKC vaccine was administered to Nile tilapia by intraperitoneal injection. The booster vaccination was conducted at 4 weeks after the first vaccination. The specific antibody titer was evaluated during rearing since the first vaccination, and then at 8 weeks after the first vaccination, the fish were challenged with A. veronii A5 and A. hydrophila A9 via intraperitoneal injection. There is not significance different in relative percentage survival of the vaccinated fish against A. veronii (63.49 ± 19.51%) and A. hydrophila (93.33 ± 6.67%). These results suggest that this candidate bivalent vaccine is effective against both A. veronii and A. hydrophila infection in Nile tilapia and could be an “motile Aeromonas septicemia (MAS)” control measure. However, to obtain the promising vaccine efficacy, the optimization of vaccine formulation might be achieved and be validated vaccine efficacy in field trial.

Efficacy of Respiratory Syncytial Virus Vaccination to Prevent Lower Respiratory Tract Illness in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

A systematic review and meta-analysis was designed in order to ascertain the effectiveness of respiratory syncytial virus (RSV) vaccination in preventing lower respiratory tract diseases (LRTD) in older adults (age ≥ 60 years). Studies reporting on randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) and the preprint repository medRxiv until 31 March 2024. A total of nine studies were eventually included, two of which were conference proceedings. Our analysis included five RCTs on five RSV vaccines (RSVpreF, RSVPreF3, Ad26.RSV.preF, MEDI7510, and mRNA-1345). The meta-analysis documented a pooled vaccine efficacy of 81.38% (95% confidence interval (95% CI) 70.94 to 88.06) for prevention of LRTD with three or more signs/symptoms during the first RSV season after the delivery of the vaccine. Follow-up data were available for RSVPreF3 (2 RSV seasons), RSVpreF (mid-term estimates of second RSV season), and mRNA-1345 (12 months after the delivery of the primer), with a pooled VE of 61.15% (95% CI 45.29 to 72.40). After the first season, the overall risk for developing RSV-related LRTD was therefore substantially increased (risk ratio (RR) 4.326, 95% CI 2.415; 7.748). However, all estimates were affected by substantial heterogeneity, as suggested by the 95% CI of I2 statistics, which could be explained by inconsistencies in the design of the parent studies, particularly when dealing with case definition. In conclusion, adult RSV vaccination was quite effective in preventing LRTD in older adults, but the overall efficacy rapidly decreased in the second season after the delivery of the vaccine. Because of the heterogenous design of the parent studies, further analyses are required before tailoring specific public health interventions.