Vaccine Efficacy Research Articles

Dynamic factors associated with COVID-19 vaccine uptake in Cameroon between 2021 and 2022.

Little is known about attitudes towards COVID-19 vaccination in sub-Saharan Africa, where immunisation coverage is the lowest in the world. The study aimed to identify factors associated with COVID-19 vaccine hesitancy and uptake in Cameroon, and assess changes in these factors over a period of time. The study was conducted in the ten regions of Cameroon. The authors conducted a two-phase cross-sectional survey in the 10 regions of Cameroon, from July 2021 to August 2021 (Phase one) and from August 2022 to September 2022 (Phase two). We analysed reasons for vaccine hesitancy descriptively and used logistic regression to assess factors associated with hesitancy. Overall, we enrolled 12 109 participants: 6567 (54.23%) in Phase one and 5542 (45.77%) in Phase two. Of these, 8009 (66.14%) were not interested in receiving the COVID-19 vaccine (n = 4176 in Phase one, n = 3833 in Phase two). The refusal rate increased significantly in the northern region from 27.00% in Phase 1 to 60.00% in Phase two. The leading contributor to COVID-19 vaccine hesitancy was fear that the vaccine was dangerous, which was significantly associated (95% confidence interval [CI], p < 0.05%) with vaccine refusal in both phases. Overall, 32.90% of participants (n = 2578) perceived the COVID-19 vaccine to be dangerous. Advanced age, male gender, Muslim religion and low level of education were associated with vaccine acceptance. Participants reported that healthcare workers were the most trusted source of information about the COVID-19 vaccine by 5005 (42.84%) participants. Despite the investment of the Ministry of Health and its partners in community engagement, focussing on communication about the vaccine efficacy, tolerance and potential adverse events, fear of the vaccine remains high, likely leading to vaccine hesitancy in Cameroon between 2021 and 2022. The study highlight regional variations in COVID-19 vaccine acceptance in Cameroon, with factors age, gender, religion and education influencing willingness to vaccine. Trust in health workers was high, indicating that, tailored, community-led vaccination strategies are key for improving vaccine uptake, not only for COVID-19 but also for future epidemics.

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.

Exploring yeast glucans for vaccine enhancement: Sustainable strategies for overcoming adjuvant challenges in a SARS-CoV-2 model

Vaccine adjuvants are important for enhancing vaccine efficacy, and although aluminium salts (Alum) are the most used, their limited ability to induce specific immune responses has spurred the search for new adjuvants. However, many adjuvants fail during product development due to manufacturability, supply, stability, or safety concerns. This work hypothesizes that protein-free yeast glucans can be used as vaccine adjuvants due to their known immunostimulatory activity and high abundancy. Thus, high molecular weight glucans with over 99% purity, comprising 64–70% β-glucans and 29–35% α-glucans, were extracted from a wild-type yeast and an engineered yeast to produce a steviol glycoside. These glucans underwent carboxymethylation to enhance solubility. Both water-dispersible and particulate glucans were evaluated as adjuvants, either alone or in combination with Alum or squalene stable emulsion (SE), for a SARS-CoV-2 vaccine. The study demonstrated that glucans triggered a robust immune response and enhanced the effects of Alum and SE when used in combination, both in vitro and in vivo. Water-dispersible glucans combined with Alum, and particulate glucans combined with SE, increased the production of specific antibodies against SARS-CoV-2 spike protein and enhanced serum neutralization titers against SARS-CoV-2 pseudovirus. Furthermore, the results indicated that larger molecular weight glucans from engineered yeast exhibited stronger immunogenic activity in comparison to wild-type yeast glucans. In conclusion, appropriately formulated glucans have the potential to be scalable, low-cost vaccine adjuvants, potentially overcoming the limitations of current adjuvants.

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.

Vaccination against RSV infections - update and perspective

Almost 60 years after a disastrous clinical vaccine trial in children, which resulted in enhanced disease and even deaths, the world of RSV vaccination is currently undergoing a dramatic positive change and development, closely linked to advances in new vaccine technologies. Three licensed safe and highly efficacious vaccines, Abrysvo, Arexvy and mRESVIA, reduce the incidence of RSV lower respiratory disease by 80% in people older than 60 years of age. Questions regarding long-term protection and effectiveness in specific risk groups with chronic medical conditions remain, and furthermore, innovative and safe concepts to actively vaccinate pregnant women and infants to prevent severe RSV infections - also in these high-risk populations - are eagerly awaited.Passive vaccination with the long-acting monoclonal antibody Nirsevimab for prevention of severe disease in the first RSV season of infants is a major innovation in global health and the importance and benefits of reducing the number of intramuscular injections for high-risk children is immense. In the coming years, results of numerous pediatric candidate RSV vaccine studies are expected, although particular caution seems advisable for historical reasons. In summary, the field of RSV vaccination has been revolutionized in the last 2 years and we will see further significant progress soon.

Insights into Genetic and Antigenic Characteristics of Influenza A(H1N1)pdm09 Viruses Circulating in Sicily During the Surveillance Season 2023-2024: The Potential Effect on the Seasonal Vaccine Effectiveness.

After disruption in the influenza circulation due to the emergence of SARS-CoV-2, the intensity of seasonal outbreaks has returned to the pre-pandemic levels. This study aimed to evaluate the evolution and variability of whole-genome sequences of A(H1N1)pdm09, the predominant influenza virus in Sicily (Italy) during the season 2023-2024. The potential vaccine efficacy was calculated using the pepitope model based on amino acid changes in the dominant epitope of hemagglutinin. The HA gene sequences showed several amino acid substitutions, some of which were within the major antigenic sites. The phylogenetic analysis showed that Sicilian strains grouped into two main genetic clades (6B.1A.5a.2a.1 and 6B.1A.5a.2a) and several subclades. Notably, about 40% of sequences partially drifted from the WHO-recommended vaccine strain A/Victoria/4897/2022 for the Northern Hemisphere. These sequences mostly belonged to the subclades C.1.8 and C.1.9 and harboured the amino acid mutations responsible for the modest predicted vaccine efficacy (E = 38.12% of 53%, pepitope = 0) against these viruses. Amino acid substitutions in other gene segments were also found. Since influenza viruses are constantly evolving, genomic surveillance is crucial in monitoring their molecular evolution and the occurrence of genetic and antigenic changes, and, thus, their potential impact on vaccine efficacy.

Provider and community perceptions of integrated COVID-19 and routine childhood immunisation programmes in Nigeria: a qualitative exploratory study

BackgroundIn Nigeria, COVID-19 vaccines were delivered through outreach activities, as well as integrated within routine immunisation. However, evaluations of integrated approaches for novel vaccines are scarce. We aimed to understand the perceived benefits and challenges of integrating the COVID-19 vaccine within routine immunisation in Nigeria, and identify ways to strengthen this approach.MethodsWe conducted 30 semi-structured interviews with community members and healthcare workers in primary healthcare facilities (PHCs) in Jigawa (n = 16) and Oyo (n = 14) states, Nigeria from 08 August to 13 September 2022. Participants were selected purposively from PHCs. We obtained information on participants’ perception about routine immunisation, and perceived benefits and challenges associated with integrated COVID-19 vaccine delivery. Healthcare worker and community interviews were analysed separately following a thematic analysis approach.ResultsWe identified four themes that describe the community and healthcare workers’ responses, perceived impact, and the health system adaptions to the challenges associated with the integrated vaccine delivery approach. Community members expressed concern that children might be given COVID-19 vaccines instead of routine immunisations, while others appreciated the integrated approach due to their trust in the efficacy of COVID-19 vaccines, government, and healthcare providers. Healthcare providers perceived the integrated approach as improving vaccination coverage and awareness but noted additional problems of increased workload, vaccine scarcity, and prolonged clinic visits. Insufficient resources were subsisting barriers to effective integration in both states, but the provider’s gender was also a challenge in Jigawa state. Additionally, the use of incentives to generate demand had ambiguous effects in Jigawa state.ConclusionTaking an integrated approach to deliver COVID-19 vaccines was acceptable by healthcare providers but community members expressed concerns. Given existing vaccination programmes have persistent challenges, it is pertinent to address these barriers to enhance effectiveness of an integrated approach.

New insights in the mechanism of the SARS-CoV-2 Mpro inhibition by benzisoselenazolones and diselenides.

Although global vaccination campaigns alleviated the SARS-CoV-2 pandemic in terms of morbidity and mortality, the ability of the virus to originate mutants may reduce the efficacy of vaccines, posing a serious risk of a renewed pandemic. There is therefore a need to develop small molecules capable of targeting conserved viral targets, such as the main protease (Mpro). Here, a series of benzisoselenazolones and diselenides were tested for their ability to inhibit Mpro; then the most potent compounds were measured for antiviral activity in vitro, and the mechanism of action was investigated. Density functional theory calculations, molecular docking and molecular dynamics simulations were also used to elucidate the protein/drug interaction. Finally, a bio-organic model was established to study the reaction between selenorganic compounds and biologically relevant thiols to unveil possible metabolic pathways of such compounds. The overall results contribute to the identification of a series of novel Se-containing molecules active against SARS-CoV-2 and to the clarification of some important aspects in the mechanisms of action of such inhibitors targeting SARS-CoV-2 Mpro.

COVID-19 – a Five-Year Update

Background: This review aims to categorically describe novel advancements to our understanding and management of COVID-19 and associated short- and long-term sequelae such as Long COVID. Methods: Indexing services (Scopus and PubMed) were used to identify pertinent studies, prioritizing original research, meta reviews and updated institutional guidelines from 2022 onwards. Papers not published in English (or where full-text translation was not available), those skewed in terms of gender distribution of participants, conducted on non-human populations and proposal and opinion papers were excluded. For the purposes of this paper, Long COVID was taken to mean the persistence of symptoms longer than 8 weeks after an acute COVID-19 infection. After deduplication, application of the exclusion criterion and checking for relevance, 52 sources were identified for this review. The keywords used for this literature search were COVID-19, Long COVID, Chronic COVID, SARS-CoV-2. Results: New COVID-19 variants challenge vaccine efficacy, highlighting socioeconomic disparities in vaccination rates. Long COVID exhibits complex symptoms, including cognitive decline and physical health impacts. The virus’s affinity for ACE-2 receptors suggests broader health implications, including reproductive and metabolic disorders. COVID-19 can cause a drop in IQ proportional to severity of disease experienced. Conclusion: COVID-19’s multifaceted health impacts necessitate ongoing research and targeted interventions. Addressing socioeconomic disparities, updating vaccine formulations, and understanding long-term effects are crucial. Equitable healthcare policies are essential to mitigate COVID-19’s global health threat and inform future strategies.

Preliminary survey of three mosquito-borne viruses using a self-established multiplex RT-qPCR assay in Chinese blood donors

BackgroundMosquito-borne pathogens pose a significant threat to both human health and blood safety. The primary mosquito-borne viruses that present this threat are Zika virus, Chikungunya virus, and Dengue virus. At present, there are limited efficacious vaccines or therapeutic drugs for the prevention and treatment of these viral infections. Blood donors can remain asymptomatically infected and unfortunately, screening for these three viruses in Chinese blood donors are not mandatory, leaving the residual risk to transfusion recipients uncertain. Objective: To address this, we developed a single-tube multiplex RT-qPCR assay for ZCD detection and was preliminarily employed to screen a total of 10,566 blood donations in Nanning Blood Center in order to assess the prevalence risk of these pathogens in blood donors. Results: None of the blood samples was reactive for ZCD by nucleic acid test (NAT). One out of 173 donations (1/173, 0.58 %) was IgG positive for ZIKV and 14 (14/173, 8.4 %) were IgG positive for DENV. None of these 173 donations was IgG positive for Chikungunya virus. These findings suggest that the prevalence of ZCD infection in blood donors in Nanning is very low although past DENV infection (IgG positive) was relatively common. Conclusion: A single-tube multiplex RT-qPCR assay for simultaneous detection of ZCD viruses was successfully established and applied for screening in blood donors. The residual risk of ZCD infection through transfusion is currently low in Nanning, China. The NAT assay for ZCD will serve as a technical reserve in response to future epidemic or pandemic of mosquito-borne pathogens.

Comparative Efficacy of Parenteral and Mucosal Recombinant Probiotic Vaccines Against SARS-CoV-2 and S. pneumoniae Infections in Animal Models.

The accumulation of specific IgG antibodies in blood serum is considered a key criterion for the effectiveness of vaccination. For several vaccine-preventable infections, quantitative indicators of the humoral response have been established, which, when reached, provide a high probability of protection against infection. The presence of such a formal correlate of vaccine effectiveness is crucial, for example, in organizing preventive measures and validating newly developed vaccines. However, can effective protection against infection occur when the level of serum antibodies is lower than that provided by parenteral vaccination? Will protection be sufficient if the same vaccine antigen is administered via mucosal membranes without achieving high levels of specific IgG circulating in the blood? In this study, we compared the immunogenicity and protective efficacy of parenteral and mucosal forms of vaccines in experimental animals, targeting infections caused by the SARS-CoV-2 coronavirus and Streptococcus pneumoniae. We investigated the protective properties of a fragment of the coronavirus S1 protein administered intramuscularly with an adjuvant and orally as part of the probiotic strain Enterococcus faecium L3 in a Syrian hamster model. A comparative assessment of the immunogenicity and protective efficacy of a recombinant tandem (PSP) of immunogenic peptides from S. pneumoniae surface proteins, administered either parenterally or orally, was performed in a Balb/c mouse model. Both models demonstrated significant differences in the immunogenicity of parenteral and oral vaccine antigens, but comparable protective efficacy.

Nationwide Discrete Choice Experiment on Chinese Guardians’ Preferences for HPV Vaccination for Mothers and Daughters

Background: HPV vaccination is the key measure to prevent cervical cancer, but uptake in China lags behind global targets. Understanding Chinese guardians’ preferences is key to improving vaccine acceptance and coverage. Methods: A nationwide online discrete choice experiment survey was conducted among 4933 Chinese guardians across seven provinces in 2022 to quantify preferences and willingness to pay. Attributes included effectiveness, safety, duration, valency, location, and out-of-pocket cost. Results: Out of the 4933 guardians who participated in the study, 4179 (84.72%) were mothers. More than 60% of the guardians belonged to the age group of 35–44 years. Additionally, over half of the respondents (53.15%) had daughters between the ages of 9 and 14 years. Respondents were open to accepting the HPV vaccine with 95% efficacy and exceptional safety. Guardians expressed a preference for longer protection duration (specifically 15 years (βa = 0.340, 95% CI: 0.31, 0.37)) and higher vaccine valency. As for willingness to pay, the respondents placed the highest value on vaccine efficacy, being willing to shell out more than USD 1100 for 95% protection as compared to 50%. Furthermore, very good safety commanded a premium of over USD 800 when compared to average safety. When it comes to willingness to uptake, a vaccine with 95% efficacy led to a more than 35% increase in acceptance as compared to one with 50% efficacy. Similarly, exceptional safety resulted in an increased willingness to uptake of over 25% when compared to average safety. Conclusions: The DCE highlighted effectiveness, safety, and durability as critical drivers of HPV vaccine acceptance, but substantial barriers persist regarding adolescent female coverage in China.

Cross-reactivity between dengue virus and SARS-CoV-2 antibodies: Confirmation study using specimens from dengue-infected patients before the COVID-19 pandemic

BackgroundThe simultaneous occurrence of the COVID-19 pandemic and a dengue outbreak has posed significant challenges for governments and medical personnel in dengue-endemic countries like Indonesia. Several studies in dengue-endemic countries have reported cases of misdiagnosis between COVID-19 and dengue. Therefore, it is crucial to evaluate the potential cross-reactivity between SARS-CoV-2 antibodies and dengue. MethodsThis study aimed to confirm the serological cross-reaction between dengue virus and SARS-CoV-2 in Surabaya, East Java, which is a highly dengue-endemic city in Indonesia. In total, 238 serum samples with confirmed dengue that were collected before the emergence of COVID-19 were tested to detect the presence of reacting IgG and IgM antibodies (Abs) against SARS-CoV-2 via a rapid detection test (RDT) and enzyme-linked immunosorbent assay (ELISA). Samples from patients with dengue infection collected during the pandemic, from healthy volunteers predating the pandemic, and from patients with COVID-19 were used for comparison. Results and conclusionFew (6.7 %) of the pre-COVID-19 dengue Ab-positive serum samples showed reactive on SARS-CoV-2 in the RDT, with significantly lower IgG and IgM levels detected in ELISA compared with the dengue samples collected during the pandemic and the COVID-19 samples (P < 0.005). A comparable anti-SARS-CoV-2 IgG concentration was observed in the pre-COVID-19 dengue samples and healthy volunteers (P = 0.56), which also indicated other possibilities. In conclusion, our results suggested a low risk of cross-reactivity between dengue virus and SARS-CoV-2. However, they highlighted the need for caution when using and interpreting data obtained stemming from serological methods, to prevent false-positive results. Further studies are needed to evaluate the cross-reactivity between dengue virus, SARS-CoV-2, and other common human pathogens, as well as its effect on the serosurveys, treatment of these diseases, or vaccine efficacy.

Abstract PR-07: Optimally designed mRNA vaccine encoding tumor-specific antigens identified in a colorectal cancer model leads to complete tumor rejection in mice

Abstract mRNA vaccines can be designed to encode multiple epitopes of choice, which is a crucial advantage when aiming to include a broad coverage immune response. Upon translation, the cell machinery must process the vaccine-encoded poly-epitope protein to release individual peptides. This processing step is key in inducing an immune response toward selected epitopes, as efficient processing yields a higher amount of peptide available for MHC-I presentation. The efficiency of peptide processing is greatly influenced by the peptide surrounding context (i.e. the flanking amino acids in N-and C-terminal). Aberrantly expressed tumor-specific antigens (aeTSAs) are MHC-I-associated peptides (MAPs) resulting from cancer-specific epigenetic changes and splicing aberrations. In contrast to TSAs derived from mutated protein-coding exons, aeTSAs are highly shared by different tumors. Moreover, unlike commonly used tumor-associated antigens (TAAs), they are not expressed by normal healthy cells, which is pivotal for inducing strong CD8+ T cell responses. The present study aimed to determine whether RNA vaccines encoding aeTSAs would elicit protective anti-tumor responses against a colorectal cancer cell line model (MC38). We hypothesized that multiepitope mRNA vaccine efficacy would be improved if the mRNA construct was composed of minimal epitopes (here, cancer antigens) bordered by optimal (rather than natural) flanking sequences. Thus, we designed 2 vaccine constructs encoding 5 aeTSAs identified by mass spectrometry in MC38 tumor cells. The 2 constructs differ in the identity of the amino acids flanking the antigens (natural vs. substituted antigen flanking sequences). Mice were injected subcutaneously with MC38 cells on Day 0. Three mRNA vaccine doses were administered intravenously one week apart, starting at Day 4. Vaccination with our improved mRNA vaccine design showed a clear therapeutic effect. As opposed to the natural flanking sequences design resulting in delayed tumor growth, vaccination with the substituted flanking sequences design led to the complete elimination of tumors and the survival of all mice. Elispot and dextramer stainings revealed that at least 3 of the 5 MC38 aeTSAs were immunogenic and that the amplitude of antigen-specific CD8+ T cell responses was significantly higher in mice vaccinated with the substituted flanking sequences design. Our results confirm our hypothesis that highly proficient flanking regions have intrinsic benefits that can be carried over to different antigens. From a translational perspective, our work provides new insights into the therapeutic potential of optimally designed aeTSA-encoding mRNA vaccines for treating cancers. Citation Format: Marie-Pierre Hardy, Krystel Vincent, Gabriel Ouellet-Lavallée, Chantal Durette, Isabelle Caron, Joel Lanoix, Mathieu Courcelles, Jean-Philippe Laverdure, Pierre Thibault, Claude Perreault. Optimally designed mRNA vaccine encoding tumor-specific antigens identified in a colorectal cancer model leads to complete tumor rejection in mice [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr PR-07.

Abstract A030: CD4 neoantigen mRNA vaccine enhances endogenous CD8 responses and tumor control

Abstract CD4 T cells have long been known to be critical for priming CD8 T cells, a process referred to as CD4 T cell help. Recent data have suggested that CD4 help may be delivered at the surface of conventional type 1 dendritic cells (cDC1s), which can efficiently present antigens (Ag) on both MHC class I and class II molecules. However, the actual mechanisms underlying CD4 T cell help remain poorly characterized. We sought to understand how anti-tumor T cell responses are generated in the context of mRNA vaccines, which have been shown to elicit protective CD4 and/or CD8 T cells. For this purpose, we compared two mRNA-Lipoplex (mRNA-LPX) vaccines that express a single MHC-II-restricted Ag either tumor-specific (neoAg) or tumor-irrelevant. mRNA-LPX is injected intravenously and taken up predominantly by cDCs in the spleen.As expected, both vaccines elicited systemic CD4 T cell responses. However, only the anti-tumor CD4 T cell response elicited the accumulation of tumor-infiltrating CD8 lymphocytes (CD8 TILs) that led to tumor regression in a CD8-dependant manner. Single cell RNA-sequencing revealed higher expression of effector molecules and genes associated with stem-like progenitor T cell states in CD8 TILs following neoAg vaccine. In contrast, inhibitory molecules were down-regulated in CD8 TILs from neoAg-vaccinated mice.We next characterized the role of cDCs in the response to the vaccines. We found that both mRNA-LPX vaccines induced better maturation of cDC1s than cDC2s in the spleen. Surprisingly, priming of CD4 T cells was dependent on cDC1s, rather than cDC2s. cDC1s were also required for neoAg CD4 vaccine-induced CD8 TIL accumulation and for vaccine efficacy. We investigated whether neoAg-specific CD4 T cells were i) sufficient to enhance anti-tumor CD8 responses and ii) needed to maintain effector CD8 TIL activity in situ. Using adoptive cell transfer (ACT) into the tumor, we found that the transfer of neoAg-specific CD4 T cells alone significantly delayed tumor growth, suggesting an increased CD8 TIL activity. Interestingly, while the transfer of CD8 TILs alone was insufficient to control tumors; ACT of both CD4 and CD8 T cells was required for efficient tumor rejection. cDC1s were required for the efficacy of both, the ACT of CD4 T cells alone and the CD4 and CD8 ACT combination. Taken together, our data suggest a novel mechanism whereby immunizing with exogenous CD4 T cell epitopes can produce tumor immunity by generating endogenous CD8 responses. These results emphasize the importance of cDC1s for both, eliciting tumor-specific CD4 T cells in the setting of mRNA-LPX vaccine expressing a single MHC-II-restricted Ag and improving in situ anti-tumor CD8 responses and tumor control. We are currently investigating the mechanisms and location of the MHC-II-restricted neoAg dependent-cDC1 help using both in vivo and cell culture approaches.This model provides fundamental insight for the development of cancer vaccines and highlights the need of tumor-specific CD4 T cells and mature tumor-Ag loaded cDC1s. Citation Format: Camille-Charlotte Balanca, Aude-Hélène Capietto, Catherine Carbone, Alan Gutierrez, Yajun Chestnut, Ellen Duong, Aditya Anand, Anthony Antonelli, Jeanne Cheung, Shiuh Luoh, Ariane Nissembaum, Keiko Hokeness, Sara Wichner, Emily Freund, Vincent Javinal, Romain Bouziat, Joshua Gober, Adel ElSohly, Jon Linehan, Ugur Sahin, Lélia Delamarre, Ira Mellman. CD4 neoantigen mRNA vaccine enhances endogenous CD8 responses and tumor control [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A030.