Vaccine Efficacy Research Articles

Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus

Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R+sM1R+sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35+ M1+ B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

SARS-CoV-2 Encephalitis versus Influenza Encephalitis: More Similarities than Differences.

From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis. The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis. A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included metaanalyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis. Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both viruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may only have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID- 19 infections (long COVID-19) have been described but not with influenza infections. Mortality associated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease. Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses.

Clinical validation of an RSV neutralization assay and analysis of cross-sectional sera associated with 2021-2023 RSV outbreaks to investigate the immunity debt hypothesis.

Population surveillance studies of serum-neutralizing activity against RSV are crucial for evaluating RSV vaccine efficacy and vulnerabilities to new strains. Here, we designed and validated a high-throughput assay for assessing anti-RSV neutralizing activity, standardized its measurements for comparison with other methodologies, and demonstrated its applicability to real-world samples. Our assay is precise, linear, and yields measurements consistent with other standardized assays, offering a methodology useful for large-scale studies of RSV immunity. We also find no significant difference in neutralizing titers among adults between those taken before and after large RSV outbreaks associated with the latter stages of the coronavirus disease of 2019 (COVID-19) public health emergency, underlining the need for a greater understanding of the dynamics of serological responses to RSV infection.

The efficacy of vaccination against respiratory syncytial virus across priority population subgroups

Abstract Background Respiratory syncytial virus (RSV) has recently become a vaccine-preventable disease as two vaccines have been approved for use and a third one is likely to become available by the end of the year. National Immunization Technical Advisory Groups as well as scientific societies across the world have issued recommendations on RSV vaccination that differ in respect to the identification of the target group. The latter has been identified in respect to age or underlying medical conditions mostly according to epidemiological data. In order to strengthen the evidence basis for future decisions, we performed a stratified meta-analysis of efficacy data considering all the three RSV vaccines currently or soon available. Methods We searched Randomized Controlled Trials (RCTs) assessing the efficacy of RSV vaccines in terms of reduction of RSV-related Lower Respiratory Tract Infection (LRTI). The research was conducted on PubMed and clinicaltrial.gov. The extraction of relevant data was stratified by pre-defined age groups (60-69, 70-79, 80+) and presence of underlying conditions increasing the risk for RSV. Results Three RCTs, one for each of the three vaccines, were considered for the quantitative analysis. Considering the overall 60+ population, the efficacy of RSV vaccines was 78% (95%CI 76-86%) in preventing LRTI. Considering the different age groups (60-69, 70-79, 80+), efficacy was respectively 72% (95%CI 53-84%), 90% (95%CI 66-97%) and 57% (95%CI 0-93%). The efficacy in healthy people and those with at least one underlying condition was similar, namely 77% (95%CI 60-87%) and 78% (95%CI 50-90%). Conclusions The available evidence shows the efficacy of RSV vaccines in reducing LRTI with no differences across different priority groups. Further studies may contribute to better understanding if the efficacy may change according to individual characteristics, that could be highly relevant in the decision-making process. Key messages • The available evidence from RCTs shows the efficacy of RSV vaccines in reducing LRTI with no differences across different priority groups. • National recommendations on RSV vaccination can be further informed for future studies investigating RSV vaccines efficacy across different subgroups.

The knowledge, attitude and practice of cardiologists versus other specialists about the safety and efficacy of influenza vaccination in patients with cardiovascular diseases

Abstract Background Influenza vaccination has been shown to reduce the occurrence of cardiovascular events, both in the general population and especially in individuals with cardiovascular disease. However, the extent to which cardiologists and other physicians support and prescribe influenza vaccination for patients with cardiovascular diseases is not known. Purpose To explore cardiologists' and other specialists' opinions on the safety and efficacy of influenza vaccination in preventing cardiovascular events. Methods From September 2023 to February 2024, a survey was conducted among physicians of any specialty, following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). The survey was available in 5 languages. Participants' opinions were assessed using Likert-type scales. Non-probabilistic convenience sampling was employed, and duplicated responses were prevented using the SurveyMonkey® platform that identifies duplicated IP addresses. Results A total of 2550 physicians from 44 countries answered the survey; the mean age was 46.1±13.1 years, 46.4% were women, and 17.1% were in training. Among respondents 43.6% were cardiologists. While 91.8% of participants considered the influenza vaccine to be very safe, and 90.6% believed that adverse effects of this intervention were rare, a significant proportion did not consider Influenza vaccine to be very beneficial in reducing acute myocardial infarction (54.4% for cardiologists vs 59.3% for other specialists, p=0.013) or stroke (62.2% for cardiologists vs 64.9% for other specialists, p=0.167). summarizes the participants’ opinions regarding the benefits and risks of influenza vaccination. Regarding potential barriers to achieving higher vaccination rates among patients with cardiovascular disease, cardiologists' opinions were similar to those of other specialists (Table 2). Patient beliefs and patients’ fear of vaccine-related adverse effects were identified as major barriers by both cardiologists and other specialists. Only 19.0% of participants reported having some type of checklist system to remind them to recommend the vaccine to their patients. While 73.0% of participants found this topic highly relevant to their daily clinical practice, with no differences between groups (p=0.178), a notable proportion, comprising 48.5% of cardiologists and 47.1% of other specialists, expressed the necessity for additional training to address the risk-benefit ratio of influenza vaccination with their patients (p=0.485). Conclusion Our data suggest that cardiologists and other specialists view the influenza vaccine as safe with a low rate of adverse effects, both in the general population and in individuals with cardiovascular disease. However, a significant proportion of them are unaware of the vaccination's benefit in reducing cardiovascular events. Additionally, about half of the surveyed professionals expressed a need for further education to discuss the benefits of vaccination with their patients.

Vaccination targeting senescence-associated transmembrane protein alleviated cardiovascular pathology in the mice

Abstract Introduction Accumulation of senescent cells is observed in various organs including vasculature, heart and white adipose tissue with age, and known to become a substrate of pathophysiology of various cardiovascular-metabolic diseases. We have previously developed a vaccine to eliminate senescent cells, so-called "senolytic vaccine" by targeting Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) as a cellular-senescence-associated cell surface protein. We have demonstrated that GPNMB senolytic vaccine could remove senescent cells and alleviate the pathology cardiovascular-metabolic diseases. Senescence-associated adhesion molecule 1 (SAAM-1) is also known as a cell-surface membrane to increase its expression during cellular senescence in endothelial cells as well as the development of cardiovascular diseases. Here, we identified SAAM-1 as another senescence antigen and created a vaccine to eliminate senescent cells by targeting SAAM-1. Purpose This study was purposed to evaluate the efficacy of SAAM-1 vaccine for the treatment of cardiovascular diseases in mice models. Methods As a pressure overload-induced heart failure (HF) model, C57BL/6N wild type (WT) mice were underwent transverse aortic constriction (TAC) or sham opretaion at 13 weeks of age. SAAM-1 or control vaccination were given at 8 and 10 weeks of age before operation. Echocardiography examination was conducted two weeks after TAC operation, followed by tissue sampling 3 weeks after the examination. As an atherosclerosis model, ApoE KO mice were subjected to a high-fat diet (HFD) starting at 4 weeks of age. Vaccination of ApoE KO mice was administered at 8 weeks of age with SAAM-1-vaccine or control-vaccine, followed by sacrifice 4 weeks later for further analysis. ApoE-KO mice were also crossed with p16-mediated Luciferase expressing mice (p16-Luc mice) and subjected to generation of atherosclerosis model. Results SAAM-1 expression was significantly increased in left ventricle (LV) in TAC mice but its increase was suppressed by SAAM-1 vaccination. Interestingly, both worsening systolic function and dilatation of LV by pressure overload were significantly alleviated by SAAM-1 vaccination. Furthermore, expression level of senescent markers including p16 and p21, as well as several inflammation markers were increased in failing heart along with development of cardiac fibrosis, but SAAM-1 vaccine could significantly attenuate this pathological change. In ApoE KO mice, SAAM-1 vaccine decreased expression level of several inflammation markers in the mice, along with a decreasing p16 signal in the aorta. Conclusions Targeting SAAM-1 for vaccination would be a novel and promising approach to alleviating age-related cardiovascular disease.

Global malaria vaccine research and community perception in Africa: a systematic review

Abstract Background Malaria vaccine is one of the critical areas in tropical health research, considering the success recorded in other vaccine-preventable diseases. This review provides an overview of global malaria vaccine research and systematically reviews community perception of the vaccine in Africa. Methods A validated search was conducted to identify scientific literature on malaria vaccines in the Scopus database from 2005. Bibliometric indicators explored include publication/citation indices over time and the overall research themes using VOSviewer. A further in-depth search was undertaken in five databases to identify studies on community perception of malaria vaccine in Africa. Studies were screened, quality appraised, and narratively synthesized. Results 6457 malaria-vaccine-related documents were found in 160 journals/sources from 189 countries/territories. There were 214,323 total citations, with 33.2 average citations per document and 167 documents’ h-index. The United States, United Kingdom and Australia combined produced more than 60% of the publication output. Six themes emerged from the global malaria vaccine research: Merozoite surface protein, characterization, trials, infant/children, traveler, and research/review. Twenty studies (n = 20) met the inclusion criteria for the systematic review. Overall perceptions of malaria vaccines varied in African communities (26.2-88.2%), in addition to higher willingness to accept the vaccines (32.3%-96.0%), poor knowledge/awareness (11%-60%) and misconceptions (19.2%-20.9%). Other issues identified include vaccine availability and logistics. Conclusions Malaria vaccine research and citations have increased considerably, mainly targeting vaccine development and safety/efficacy in Africa. African communities’ perceptions of the vaccine varied, with most of the population willing to accept the vaccine. Key messages • An increase in number of malaria vaccine research targeting vaccine development, and safety and efficacy in Africa. • Varried malaria vaccine perception in Africa, including willingness to accept the vaccine, awareness, misconceptions, availability and logistics.

Artificial intelligence – NPHIs’ role in utilizing its opportunities and addressing the risks

Abstract Issue & Problem National Public Health Institutes (NPHIs) in many countries are at the forefront of action to mitigate the impact of current and future threats to health as well as improving population health and wellbeing. Through research, collaboration, and support, NPHIs can approach these new realities together. One of the many emerging realities that NPHIs will need to engage in is how NPHIs best can utilise the powers of artificial intelligence and deal with the ethical and legal issues that come with it. Methods In preparation of IANPHI’s (International Association of National Public Health Institutes) Europe Regional network meeting in April 2024 a survey was conducted among the 42 members. 16 countries replied to questions, around e.g., 1) current applications of (generative) artificial intelligence (AI) in the work of institutes, 2) which experiences were made and 3) which measures NPHIs take to best utilize the possibilities and overcome challenges of AI technologies. Within four weeks 16 replies were shared. Lessons & Conclusions Some institutes have not yet adopted AI, while others report multiple applications but the primary areas of application vary considerably among Europe. Applications include summarizing and reformatting text; translation; transcribing and documenting meetings; search information in documents or databases; coding; creating visuals; literature review; surveillance of infectious diseases; disease forecasting; analysis of transmission dynamics; vaccine efficacy assessment and development; image recognition; diagnosis and prediction of diseases from medical datasets; text mining; symptom extraction; social listening; prediction of nitrate concentration in groundwater; drug analysis and measuring psychological resilience in social crisis. Key messages • AI poses opportunities and risks for public health and work of national public health institutes and capacity building initiatives are essential. • IANPHI decided to develop a joint framework for the use of AI in its member organisations with a focus on research and responsible use.

Assessing the impact of a potential canine vaccine for the control of Chagas disease: a mathematical modeling study

IntroductionChagas disease, a zoonotic infection transmitted by triatomine bugs, poses serious public health risks in endemic areas. As dogs are important reservoirs in the disease’s spread, developing a canine vaccine could be transformative for controlling disease transmission to dogs and humans.MethodsWe developed a compartmental Susceptible-Infected model to simulate the transmission dynamics of Trypanosoma cruzi, considering interactions among dogs, humans, cats, rodents, and triatomine vectors. We used the model to assess the direct and indirect impacts of two vaccine mechanisms—all-or-nothing and leaky—on disease incidence across different host populations. The sensitivity of the model’s outcomes to changes in input parameters was analyzed using univariate sensitivity analysis.ResultsOur model showed that with a 90% vaccine efficacy, an all-or-nothing vaccine could reduce the cumulative incidence of T. cruzi in dogs by 91.3% over five years. The 60% and 30% vaccine efficacies would result in reductions of 63.47% and 33%, respectively, over 5 years. Similarly, the leaky vaccine achieved a 92.62% reduction in dog infections over 5 years with 90% efficacy. The indirect effects on human T. cruzi infection were notable; the all-or-nothing vaccine reduced human disease incidence by 14.37% at 90% efficacy, while the leaky vaccine achieved a 32.15% reduction over 5 years. Both vaccine mechanisms may substantially reduce T. cruzi incidence among dogs, and generate indirect benefit to other hosts, such as humans, by reducing their infection risk. The indirect benefits of vaccination were heavily influenced by the proportion of triatomine bugs blood meals taken from dogs.DiscussionThe study highlights the potential of targeted canine vaccination in controlling Chagas disease transmission and burden in endemic countries. It provides additional evidence for pursuing the development of a canine vaccine as a valuable tool for Chagas disease elimination.

Effect of RTS,S/AS01E vaccine booster dose on cellular immune responses in African infants and children

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).

Adjuvant potential of Peyssonnelia caulifera extract on the efficacy of an influenza vaccine in a murine model

Natural adjuvants have recently garnered interest in the field of vaccinology as their immunostimulatory effects. In this study, we aimed to investigate the potential use of Peyssonnelia caulifera (PC), a marine alga, as a natural adjuvant for an inactivated split A/Puerto Rico/8/1934 H1N1 influenza vaccine (sPR8) in a murine model. We administered PC-adjuvanted vaccines to a murine model via intramuscular prime and boost vaccinations, and subsequently analyzed the induced immunological responses, particularly the production of antigen-specific IgG1 and IgG2a antibodies, memory T and B cell responses, and the protective efficacy against a lethal viral infection. PC extract significantly bolstered the vaccine efficacy, demonstrating balanced Th1/Th2 responses, increased memory T and B cell activities, and improved protection against viral infection. Notably, within 3 days post-vaccination, the PC adjuvant stimulated activation markers on dendritic cells (DCs) and macrophages at the inguinal lymph nodes (ILN), emphasizing its immunostimulatory capabilities. Furthermore, the safety profile of PC was confirmed, showing minimal local inflammation and no significant adverse effects post-vaccination. These findings contribute to our understanding of the immunomodulatory properties of natural adjuvants and suggest the promising roles of natural adjuvants in the development of more effective vaccines for infectious diseases.

Immunogenicity and Efficacy of Combined mRNA Vaccine Against Influenza and SARS-CoV-2 in Mice Animal Models

Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. Objectives. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. Methods. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. Results. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. Conclusions. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza.

Behaviorally informed digital campaigns and their association with social media engagement and COVID-19 vaccine uptake in Belize

BackgroundIncreasing vaccination coverage was key to curbing the COVID-19 pandemic globally. However, lack of trust in the vaccine and fear of side effects in regions like the Caribbean resulted in a low uptake despite enough vaccine supply.MethodsWe conducted two correlational analyses and one experiment between five sequential behaviorally informed Facebook campaigns, social media performance outcomes, and district-level vaccination data. First, we ran multivariate linear regression models to estimate the mean differences between the campaigns in (i) social media performance (“Clicks” and “Engagement”) and (ii) COVID-19 vaccination uptake at the district level. “Clicks” were measured by the number of people who clicked on the respective Facebook advert and visited the official vaccination site. “Engagements” were the number of people interacting with the advert through likes and emojis. Second, we took advantage of the experimental design during one of the campaigns to analyze the differential effect of messages conveying information about the number of people reporting vaccination side effects using words (“Few”/ “Majority) and numbers (“3 out of 100 “) on social media performance.ResultsThe correlational analysis showed that the number of “Clicks” and “Engagement” was similar among campaigns, except for the campaign focusing on vaccines’ effectiveness, which had 14.65 less clicks and 19.52 less engagements per advert (including controls and district-fixed effects) compared to the base “It’s safe” campaign. Vaccination rates were highest at times coinciding with campaigns focusing on vaccination safety and effectiveness. Our experimental results showed that informational messages related to side effects that were framed using words (“Majority did not report discomfort”/ “Few persons reported discomfort”) were better at generating “Clicks” compared to those using numbers (“3 out of 100 reported discomforts”).ConclusionsFacebook adverts highlighting vaccine safety had a similar level of social media performance as other campaigns, except for adverts focusing on vaccine efficacy, which performed worse. Communicating side-effect information with words instead of numbers can expand social media interest in low-uptake regions like the Caribbean. Our results serve as preliminary evidence for public health officials to encourage vaccine uptake in high-hesitancy contexts.

Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors.

Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

CpG-adjuvanted virus-like particle vaccine induces protective immunity against Leishmania donovani infection.

Visceral leishmaniasis (VL) poses a significant public health challenge due to the lack of an approved human vaccine. We attempted to enhance the efficacy of virus-like particle vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA-VLP) by adjuvanting with CpG oligodeoxynucleotide (CpG-ODN). Here, adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L. donovani promastigotes were evaluated. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG, IgG1, IgG2a, and IgG2b serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T cell activities, compared to unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines IFN-γ and IL-6 in visceral organs, leading to decreased total parasite burden and protection against L. donovani challenge. Our findings indicate that CpG-ODN enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective VL vaccine development.

Characterization of Luciferase from Photorhabdus kayaii and its Application for In vivo Imaging Studies in Mice.

Bioluminescence, or the production of light by luciferases, is the basis of a well-known reporter technology. A quick way to study the efficacy of antimicrobial drugs and vaccines is in vivo bioluminescence imaging (BLI). Photorhabdus spp. represent the only terrestrial group of bioluminescent bacteria. The luciferase obtained from Photorhabdus luminescence has been widely used in BLI studies. However, little information is available about the functions of luciferases obtained from other members of this genera. This study aimed to evaluate the applicability of the luciferase obtained from Photorhabdus kayaii for BLI studies. P. kayaii starE, an Iranian isolate of P. kayaii, was cultivated on NBTA agar plates. The resulting colonies were cultured on McConkey agar to determine the bacterial phase. Bioluminescence emission was measured using a multimode reader. The luciferase genes of this bacterium were sequenced following the PCR amplification, and the corresponding amino acid sequences were determined. The luciferase tertiary structure was then obtained from the TACOS web server and compared to that of P. luminescence in CE software. The lux operon encoding the luciferase (luxA and luxB genes) and substrate synthesis complex was cloned and expressed in Escherichia coli BL21 (DE3) using the pBBR1MCS2_START vector. The luminescence emission during the growth was examined. Moreover, the effects of pH and sodium deoxycholate (bile salt) on bioluminescence emission were investigated. Appropriate conditions for the use of bioluminescent E. coli for BLI studies in mice were demonstrated in terms of cell numbers and injection routes. The bacterium was luminescent and in phase I. Its luciferase monomers (α and β) shared 100% amino acid homology with P. kayaii M-HU2 and more than 92% with P. luminescence. Tertiary structures of the luciferase monomers were 93%- 95% identical to those of P. luminescence. The lux operon was expressed in E. coli, and the maximum bioluminescence signal was observed during the decelerating phase of growth. The bioluminescence at different pH values correlated with the cell survival. The luminescence was emitted by cells exposed to the bile salt. A strong bioluminescent signal was emitted from mice after subcutaneous injection of bioluminescent E. coli at 107 CFU. However, no signals were emitted from mice that were administered the same cell number via intraperitoneal injection. A 2.5-fold increase in the cell number resulted in bioluminescence detection in the abdomen of mice after intraperitoneal injection and a 3.22-fold increase in signal intensity after subcutaneous injection. These results demonstrated the usefulness of P. kayaii luciferase for BLI studies.

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

Immunogenicity and efficacy of XBB.1.5 rS vaccine against the EG.5.1 variant of SARS-CoV-2 in Syrian hamsters.

As SARS-CoV-2 continues to evolve, there is a need to assess the immunogenicity and efficacy of updated vaccines against newly emerging variants in pre-clinical models such as mice and hamsters. Here, we compared the immunogenicity and efficacy between the updated XBB.1.5, the original Prototype Wuhan-1, and the bivalent Prototype + BA.5 vaccine against a challenge with the EG.5.1 Omicron variant of SARS-CoV-2 in hamsters. The XBB.1.5 and bivalent vaccine, but not the Prototype, induced serum-neutralizing antibodies against EG.5.1, albeit the titers were higher in the XBB.1.5 immunized hamsters. The presence of neutralizing antibodies was associated with complete protection against EG.5.1 infection in the lower airways and reduced virus titers in the upper airways. Compared with the bivalent vaccine, immunization with XBB.1.5 improved viral control in the nasal turbinates. Together, our data show that the updated vaccine is immunogenic and that it offers better protection against recent variants of SARS-CoV-2.

Triton X-100-treated virus-based ELLA demonstrates discordant antigenic evolution of influenza B virus hemagglutinin and neuraminidase.

Neuraminidase (NA)-specific antibodies have been associated with protection against influenza and thus NA is considered a promising target for next-generation vaccines against influenza A (IAV) and B viruses (IBV). NA inhibition (NI) by antibodies is typically assessed using an enzyme-linked lectin assay (ELLA). However, ELLA can be confounded by anti-hemagglutinin (anti-HA) antibodies that block NA by steric hindrance (termed HA interference). Although strategies have been employed to overcome HA interference for IAV, similar approaches have not been assessed for IBV. We found that HA interference is common in ELLA using IBV, rendering the technique unreliable. Anti-HA antibodies were not completely depleted from sera by HA-expressing cell lines, and this approach was of limited utility. In contrast, we find that treatment of virions with Triton X-100, but not Tween-20 or ether, efficiently separates the HA and NA components and overcomes interference caused by anti-HA antibodies. We also characterize a panel of recombinant IBV NA proteins that further validated the results from Triton X-100-treated virus-based ELLA. Using these reagents and assays, we demonstrate discordant antigenic evolution between IBV NA and HA over the last 80 years. This optimized ELLA protocol will facilitate further in-depth serological surveys of IBV immunity as well as antigenic characterization of the IBV NA on a larger scale.IMPORTANCEInfluenza B viruses (IBVs) contribute to annual epidemics and may cause severe disease, especially in children. Consequently, several approaches are being explored to improve vaccine efficacy, including the addition of neuraminidase (NA). Antigen selection and assessment of serological responses will require a reliable serological assay to specifically quantify NA inhibition (NI). Although such assays have been assessed for influenza A viruses (IAVs), this has not been done of influenza B viruses. Our study identifies a readily applicable strategy to measure the inhibitory activity of neuraminidase-specific antibodies against influenza B virus without interference from anti-hemagglutinin (anti-HA) antibodies. This will aid broader serological assessment of influenza B virus-specific antibodies and antigenic characterization of the influenza B virus neuraminidase.