Vaccines, Volume 11, Issue 9 (September 2023) – 117 articles

Streptococcus pyogenes (group A Streptococcus; GAS), a Gram-positive coccal bacterium, poses a significant global disease burden, especially in low- and middle-income countries. Its manifestations can range from pharyngitis and skin infection to severe and aggressive diseases, such as necrotizing fasciitis and streptococcal toxic shock syndrome. At present, although GAS is still sensitive to penicillin, there are cases of treatment failure for GAS pharyngitis, and antibiotic therapy does not universally prevent subsequent disease. In addition to strengthening global molecular epidemiological surveillance and monitoring of antibiotic resistance, developing a safe and effective licensed vaccine against GAS would be the most effective way to broadly address GAS-related diseases. Over the past decades, the development of GAS vaccines has been stalled, mainly because of the wide genetic heterogeneity of GAS and the diverse autoimmune responses to GAS. With outbreaks of scarlet fever in various countries in recent years, accelerating the development of a safe and effective vaccine remains a high priority. When developing a GAS vaccine, many factors need to be considered, including the selection of antigen epitopes, avoidance of self-response, and vaccine coverage. Given the challenges in GAS vaccine development, this review describes the important virulence factors that induce disease by GAS infection and how this has influenced the progression of vaccine development efforts, focusing on several candidate vaccines that are further along in development. Full article

COVID-19 vaccines were developed at an unprecedented speed in history. The factors affecting the response to COVID-19 vaccines are not clear. Herein, the effects of vitamin D and vitamin A (retinol) levels on the response to the BNT162b2 vaccine were explored. A total of 124 vaccine recipients were recruited from the general population attending vaccination centers in Irbid, Jordan. Blood samples were collected immediately before receiving the first vaccine dose (D0) and three weeks later (D21). Baseline (D0) levels of 25-hydroxyvitamin D [25(OH)D], retinol, and SARS-CoV-2 S1 IgG antibodies were measured with ELISA. The response to the BNT162b2 vaccine was tested by measuring the levels and avidity of SARS-CoV-2 S1 IgG antibodies on D21. The participants were divided into two groups, unexposed and exposed, based on the D0 SARS-CoV-2 antibody results. No significant correlation was found between the levels of 25(OH)D or retinol and the levels, avidity, or fold increase of antibodies in both groups. Similarly, no significant difference in antibody response was found between 25(OH)D status groups, retinol status groups, or combined status groups. These findings show that the baseline vitamin D or vitamin A levels have no effect on the short-term response to a single dose of BNT162b2 vaccine. Full article

Background: Vaccination against seasonal influenza has proven effective in preventing nosocomial influenza outbreaks among hospital patients and healthcare workers (HCWs). This study aims to explore the intention, motivation, and empowerment toward vaccination and vaccination advocacy as contributing factors for seasonal influenza vaccination in HCWs. Methods: A cross-sectional study in eight secondary hospitals in Greece was conducted from March to May 2022. An anonymous questionnaire was enclosed in an envelope and distributed to all participants, including questions on vaccine behavior and the MoVac-flu and MoVad scales. Results: A total of 296 participants completed the questionnaire. In multivariate logistic regression models adjusted for potential confounders, increased age, intention score, MoVac-flu scale score, and the presence of chronic diseases were significant predictors of influenza vaccination this year, while increased age, intention score, and presence of chronic diseases were predictors of vaccination every year. Conclusion: Vaccination uptake is simultaneously affected by logical cognitive processes (intention), together with factors related to motivation and empowerment in distinct self-regulatory domains such as value, impact, knowledge, and autonomy. Interventions focused on these identified predictors may be used as a guide to increase HCWs’ vaccination rates. Full article

Vaccine-preventable diseases (VPDs) remain a significant public health challenge, particularly in sub-Saharan Africa. The high burden of VPDs in this region necessitates the need for continued investigation and intervention. This paper presents a bibliometric analysis of research on VPDs in children in sub-Saharan Africa in the last 10 years to capture the current state of research in the field. This study used a systematic search for articles published between 2013 and 2022 in the Web of Science Core Collection database and, subsequently, scientometric techniques for data analyses and interpretation. Annual scientific production of publications on the research of VPDs in children in sub-Saharan Africa increased from 2013 to 2019 and then gradually declined. South Africa had the most VPD studies (n = 148; 16.2%), followed by Nigeria, Ghana, Kenya, The Gambia, Malawi, Ethiopia, and the Republic of Congo. The Vaccine journal published the most. The Pan African Medical Journal was the most frequent destination journal based in Africa. The commonly studied pathogens were Streptococcus pneumoniae and Haemophilus influenzae. Research productivity increased exponentially in the pre-COVID era and declined in the past two years, so more VPD research in this region is needed. Full article

Recently, a great effort has been devoted to studying attenuated and subunit vaccine development against SARS-CoV-2 since its outbreak in December 2019. It is known that diverse virus-like particles (VLPs) are extensively employed as carriers to display various antigenic and immunostimulatory cargo modules for vaccine development. Single or multiple antigens or antigenic domains such as the spike or nucleocapsid protein or their variants from SARS-CoV-2 could also be incorporated into VLPs via either a genetic or chemical display approach. Such antigen display platforms would help screen safer and more effective vaccine candidates capable of generating a strong immune response with or without adjuvant. This review aims to provide valuable insights for the future development of SARS-CoV-2 VLP vaccines by summarizing the latest updates and perspectives on the vaccine development of VLP platforms for genetic and chemical displaying antigens from SARS-CoV-2. Full article

Background: Despite the high vaccination coverage rate, in-hospital transmission of measles continues to occur in South Korea. We present a measles outbreak in which two healthcare workers (HCWs) with presumptive evidence of measles immunity were infected by a patient with typical measles at a single hospital in South Korea. This facilitated the evaluation of measles seroprevalence in all HCWs. Methods: In 2018, suspected patients and contacts exposed during a measles outbreak were investigated based on their medical histories and vaccination status. Cases were confirmed by the detection of measles-specific immunoglobulin M or RNA. After the measles outbreak in 2018, measles IgG testing was conducted on a total of 972 HCWs for point-prevalence, including those exposed to the measles. In addition, we have routinely performed measles IgG tests on newly employed HCWs within one week of their hire date since 2019. The measles vaccine was administered to HCWs who tested negative or equivocally negative for IgG antibodies. Results: An index patient who returned from China with fever and rash was diagnosed with measles at a hospital in Korea. Two additional HCWs were revealed as measles cases: one was vaccinated with the two-dose measles–mumps–rubella (MMR) vaccine, and the other, who was born in 1967, was presumed to have immunity from natural infection in South Korea. All three patients harbored the same D8 genotype. No additional measles cases were identified among the 964 contacts of secondary patients. A total of 2310 HCWs, including those tested during the 2018 outbreak, underwent measles IgG tests. The average age at the time of the test was 32.6 years, and 74.3% were female. The overall seropositivity of measles was 88.9% (95% confidence interval, 87.5–90.1). Although the birth cohorts between 1985 and 1994 were presumed to have received the measles–rubella (MR) catch-up vaccination in 2001, 175 (89.3%) HCWs were born after 1985 among the 195 seronegative cases. Conclusion: Despite high population immunity, imported measles transmission occurred among HCWs with presumed immunity. This report underscores the importance of understanding the prevalence of measles susceptibility among newly employed HCWs. This is important for policymaking regarding hospital-wide vaccinations to prevent the spread of vaccine-preventable diseases. Full article

Group A streptococcus (GAS) is a global pathogen associated with significant morbidity and mortality for which there is currently no licensed vaccine. Vaccine development has been slow, mostly due to safety concerns regarding streptococcal antigens associated with autoimmunity and related complications. For a GAS vaccine to be safe, it must be ensured that the antigens used in the vaccine do not elicit an antibody response that can cross-react with host tissues. In this study, we evaluated the safety of our GAS vaccine candidate called VaxiStrep in New Zealand White rabbits. VaxiStrep is a recombinant fusion protein comprised of streptococcal pyrogenic exotoxin A (SpeA) and exotoxin B (SpeB), also known as erythrogenic toxins, adsorbed to an aluminum adjuvant. The vaccine elicited a robust immune response against the two toxins in the rabbits without any adverse events or toxicity. No signs of autoimmune pathology were detected in the rabbits’ brains, hearts, and kidneys via immunohistochemistry, and serum antibodies did not cross-react with cardiac or neuronal tissue proteins associated with rheumatic heart disease or Sydenham chorea (SC). This study further confirms that VaxiStrep does not elicit autoantibodies and is safe to be tested in a first-in-human trial. Full article

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, the cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. However, the cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with ovalbumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lymphoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity. Full article

The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors. Full article

In vaccine efficacy trials, inaccurate counting of infection cases leads to systematic under-estimation—or “dilution”—of vaccine efficacy. In particular, if a sufficient fraction of observed cases are false positives, apparent efficacy will be greatly reduced, leading to unwarranted no-go decisions in vaccine development. Here, we propose a range of replicate testing strategies to address this problem, considering the additional challenge of uncertainty in both infection incidence and diagnostic assay specificity/sensitivity. A strategy that counts an infection case only if a majority of replicate assays return a positive result can substantially reduce efficacy dilution for assays with non-systematic (i.e., “random”) errors. We also find that a cost-effective variant of this strategy, using confirmatory assays only if an initial assay is positive, yields a comparable benefit. In clinical trials, where frequent longitudinal samples are needed to detect short-lived infections, this “confirmatory majority rule” strategy can prevent the accumulation of false positives from magnifying efficacy dilution. When widespread public health screening is used for viruses, such as SARS-CoV-2, that have non-differentiating features or may be asymptomatic, these strategies can also serve to reduce unneeded isolations caused by false positives. Full article

Background: The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, paralleling the aging of the population. cSCC predominantly affects chronically sun-exposed areas, such as the head and neck region. At our tertiary center, a multidisciplinary approach to non-melanoma skin cancer is provided for locally advanced cSCC. Methods: We retrospectively revised all patients with locally advanced/metastatic cSCC treated with anti-PD1 antibody (Cemiplimab) at our Institution from January 2020 to March 2023 (minimum follow-up of 4 months on treatment). Results: Overall, we consecutively treated 20 ultra-octogenarian patients, of whom 15 were males and 5 were females (median age: 86.9 years). Despite age, a median number of concomitant drugs, and comorbidities, efficacy, and safety were superimposable with the available literature. No patients reported treatment-related adverse events of grade 3 or higher. Grade 2 adverse events were reported in 25% of patients. Overall, the response rate was 65%, with 50% partial responses and 20% long-lasting stable disease. The median duration of response was 14 months. The G8 elderly score was assessed in all patients, and the median score was 12 (range 9–14). Conclusions: Among ultra-octogenarian patients, a clinical benefit from Cemiplimab was obtained in most, including tumor shrinkage and pain relief. Cemiplimab confirmed its effectiveness in elderly patients in a real-life setting, with no new safety concerns. Full article

Many highly effective vaccines have been developed to protect dogs against disease caused by canine parvovirus, but despite this vaccine interference by maternally derived antibodies continues to cause immunisation failure. To help overcome this limitation we have developed a novel, recombinant canine parvovirus type 2c vaccine strain, based on the structural and non-structural elements of an established type 2 vaccine. This novel CPV-2c vaccine strain has unique efficacy in the field, it is able to induce sterilising immunity in naïve animals 3 days after vaccination and is able to overcome very high levels of maternally derived antibodies from 4 weeks of age—thus closing the immunity gap to canine parvovirus infection in young puppies. The vaccine strain, named 630a, has been combined with an established canine distemper virus Onderstepoort vaccine strain to produce a new bivalent vaccine (Nobivac DP PLUS), intended to immunise very young puppies in the face of high levels of maternally derived antibody. Here, we describe the onset of immunity and maternal antibody interference studies that support the unique efficacy of the strain, and present overdose studies in both dogs and cats that demonstrate the vaccine to be safe. Full article

Fowl cholera is caused by the bacterium Pasteurella multocida, a highly transmissible avian ailment with significant global implications, leading to substantial economic repercussions. The control of fowl cholera outbreaks primarily relies on vaccination using traditional vaccines that are still in use today despite their many limitations. In this research, we describe the development of a genetically engineered herpesvirus of turkeys (HVT) that carries the OmpH gene from P. multocida integrated into UL 45/46 intergenic region using CRISPR/Cas9-NHEJ and Cre-Lox system editing. The integration and expression of the foreign cassettes were confirmed using polymerase chain reaction (PCR), indirect immunofluorescence assays, and Western blot assays. The novel recombinant virus (rHVT-OmpH) demonstrated stable integration of the OmpH gene even after 15 consecutive in vitro passages, along with similar in vitro growth kinetics as the parent HVT virus. The protective efficacy of the rHVT-OmpH vaccine was evaluated in vaccinated ducks by examining the levels of P. multocida OmpH-specific antibodies in serum samples using ELISA. Groups of ducks that received the rHVT-OmpH vaccine or the rOmpH protein with Montanide™ (SEPPIC, Paris, France) adjuvant exhibited high levels of antibodies, in contrast to the negative control groups that received the parental HVT or PBS. The recombinant rHVT-OmpH vaccine also provided complete protection against exposure to virulent P. multocida X-73 seven days post-vaccination. This outcome not only demonstrates that the HVT vector possesses many characteristics of an ideal recombinant viral vaccine vector for protecting non-chicken hosts, such as ducks, but also represents significant research progress in identifying a modern, effective vaccine candidate for combatting ancient infectious diseases. Full article

This study aimed to evaluate the efficacy of a virus-like particle (VLP) vaccine containing the open reading frame 2 of porcine circovirus type 2d (PCV2d) in a farm environment where natural infections associated with porcine circovirus-associated disease are endemic. The vaccine trial was conducted on three farms (H, M, and Y) with a history of infections including porcine reproductive and respiratory syndrome virus (PRRSV), PCV, Mycoplasma, and E. coli. Farm H, as well as farms M and Y, experienced natural PCV2 infection between 4 and 8 weeks post-vaccination (wpv), and 8 and 12 wpv, respectively. Viremia levels of all farms were significantly (p < 0.05) lower in vaccinated piglets than the control group after natural infection. In all farms, serum immunoglobulin G levels peaked at 8 wpv in the vaccinated groups, surpassing those in the control groups. Furthermore, neutralizing antibody titers were significantly (p < 0.05) higher in the vaccinated groups than the control groups in farms H and Y (0–8 wpv). However, there were no significant differences between the vaccinated and control group in neutralizing antibody titers of farm M (0–20 wpv). In terms of body weight, vaccinated piglets from all three farms showed significantly increased average weights at 12 wpv compared to the control groups. In conclusion, our study revealed noteworthy differences in viremia and body weight gain between vaccinated and control animals on three farms. As a result, this field trial of PCV2d VLP vaccine was successful in protecting piglets from natural PCV2 infection. Full article

Vaccination has been the most effective way to control the outbreak of the COVID-19 pandemic. The numbers and types of vaccines have reached considerable proportions, even if the question of vaccine procedures and frequency still needs to be resolved. We have come to learn the necessity of defining vaccination distribution strategies with regard to COVID-19 that could be used for any future pandemics of similar gravity. In fact, vaccine monitoring implies the existence of a strategy that should be measurable in terms of input and output, based on a mathematical model, including death rates, the spread of infections, symptoms, hospitalization, and so on. This paper addresses the issue of vaccine diffusion and strategies for monitoring the pandemic. It provides a description of the importance and take up of vaccines and the links between procedures and the containment of COVID-19 variants, as well as the long-term effects. Finally, the paper focuses on the global scenario in a world undergoing profound social and political change, with particular attention on current and future health provision. This contribution would represent an example of vaccination experiences, which can be useful in other pandemic or epidemiological contexts. Full article

Workers occupationally exposed to welding dusts and fumes have been suspected to be at increased risk of invasive pneumococcal disease (IPD). Since the 2010s, the United Kingdom Department of Health and the German Ständige Impfkommission (STIKO) actively recommend welders undergo immunization with the 23-valent polysaccharide (PPV23) pneumococcal vaccine, but this recommendation has not been extensively shared by international health authorities. The present meta-analysis was therefore designed to collect available evidence on the occurrence of pneumococcal infection and IPD among welders and workers exposed to welding fumes, in order to ascertain the effective base of evidence for this recommendation. PubMed, Embase and MedRxiv databases were searched without a timeframe restriction for the occurrence of pneumococcal infections and IPD among welders and workers exposed to metal dusts, and articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 854 entries, 14 articles (1.6%) underwent quantitative analysis, including eight retrospective studies (publication range: 1980–2010), and six reports of professional clusters in shipbuilding (range: 2017–2020). Welders had an increased likelihood of developing IPD compared with non-welders (odds ratio 2.59, 95% CI 2.00–3.35, I² = 0%, p = 0.58), and an increased likelihood of dying from IPD (standardized mortality ratio (SMR) 2.42, 95% CI 1.96-2.99, I² = 0%, p = 0.58). Serotype typing was available for 72 cases, 60.3% of which were represented by serotype 4, followed by 12F (19.2%) and serotype 8 (8.2%). Although the available data derive from a limited number of studies, available results suggest that pneumococcal vaccination should be recommended for workers exposed to welding fumes, and vaccination strategies should consider the delivery of recombinant formulates in order to combine the direct protection against serotypes of occupational interest with the mucosal immunization, reducing the circulation of the pathogen in occupational settings characterized by close interpersonal contact. Full article

The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG) were isolated from the blood of COVID-19 patients vaccinated with Sputnik V. The fractions were analyzed for their potential to hydrolyze 18-mer oligopeptides corresponding to linear fragments of the SARS-CoV-2 S-protein. Here, we show that the IgG antibodies hydrolyze six out of nine oligopeptides efficiently, with the antibodies of COVID-19-exposed donors demonstrating the most significant activity. The IgGs of control donors not exposed to SARS-CoV-2 were found to be inactive in oligopeptide hydrolysis. The antibodies of convalescents and vaccinated patients were found to hydrolyze oligopeptides in a wide pH range, with the optimal pH range between 6.5 and 7.5. The hydrolysis of most oligopeptides by RBD-IgG antibodies is inhibited by thiol protease inhibitors, whereas S-IgG active centers generally combine several types of proteolytic activities. Ca²⁺ ions increase the catalytic activity of IgG preparations containing metalloprotease-like active centers. Thus, the proteolytic activity of natural antibodies against the SARS-CoV-2 protein is believed to be due to the similarity of catalytic antibodies’ active centers to canonical proteases. This work raises the question of the possible physiological role of proteolytic natural RBD-IgG and S-IgG resulting from vaccination and exposure to COVID-19. Full article

The arrival of specific vaccines was crucial for the eradication of COVID-19. Despite the security of the vaccination, the administration of COVID-19 mRNA vaccines often causes systemic side effects for a short time after the injection, such as headache, fatigue, fever, muscle pain and nausea. These side effects can limit the adherence to COVID-19 vaccines administration, especially in healthcare workers. This study aims to analyze the impact of the prophylactic use of paracetamol to reduce the post-vaccination Comirnaty/Pfizer adverse effects. The study took place at the San Giovanni Battista Hospital in Rome and included all hospital employees who received two doses of Pfizer-BioNTech. The vaccination health personnel recommended the preventive intake of 1 g of paracetamol before the inoculation of the vaccine and then every 6 h in the first 24 h. Information was collected through forms and subsequent telephone recall. A total of 403 volunteers were involved in the study, with 391 of them receiving two doses and twelve individuals only one dose of the vaccine. The main results demonstrated that the prophylactic therapy influenced the lower onset of asthenia in the first and second doses. However, there were no significant differences between the two groups in terms of fever, headache and localized pain. Paracetamol had a good impact on the side effect of COVID-19 vaccination, reducing asthenia in both doses and mitigating the total of symptoms during the second vaccination. Full article

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3–12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty^® (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4⁺ T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty^®-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations. Full article

Vaccination plays a crucial role in combating the global COVID-19 pandemic. Immunizing all healthcare workers (HCWs) is essential for increasing vaccine confidence and acceptance within the general population. Understanding the factors that hinder or facilitate vaccine uptake among HCWs is of utmost importance, considering they are among the first to be vaccinated. This review follows Arksey and O’Malley’s five-stage methodological framework. We searched PubMed, Web of Science, ProQuest, WorldCat Discovery, and Google Scholar for peer-reviewed articles published from 2020 to 2023. A descriptive analysis and narrative synthesis approach were employed to collect and synthesize data. Using the social-ecological model as a framework, the literature was categorized into themes at the intrapersonal, interpersonal, organizational, community, and policy levels. We reviewed a total of fifty-three published academic articles, with the majority of studies conducted in Ethiopia and Nigeria. The intention for vaccine uptake resulted in an unsatisfactory (52%) overall uptake rate among HCWs. Individual-level determinants associated with vaccine uptake included being male, middle-aged, being a physician, having a higher level of education, and having a chronic illness. This review identified significant barriers at each level, such as safety concerns, perceived scientific uncertainty, vaccine ineffectiveness, lack of trust in stakeholders, and religious beliefs. Additionally, we identified facilitators at each level, with the most common factors promoting intention to uptake being the desire to protect oneself and others and a high perceived susceptibility to contracting COVID-19. This review highlights the existence of significant barriers to vaccine uptake on the African continent. Given that HCWs play a crucial role in guiding the public’s vaccination decisions, it is imperative to prioritize education and training efforts about the safety and effectiveness of COVID-19 vaccines. Full article

cSCC (cutaneous squamous cell carcinoma) and its precursors are a major cause of morbidity, especially in immunosuppressed patients, and are frequently associated with human papillomavirus (HPV) infections. The purpose of this study is to investigate the therapeutic potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. In this retrospective study, all patients who received Gardasil-9^®, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated Poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14–0.51, p < 0.001) between pre- and post-Gardasil-9^® intervention. Gardasil-9^® vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 caseloads during the observational period. Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions and overall mortality as well as healthcare costs in immunosuppressed patients with high skin tumor burden. Full article

Background: In developing countries, access to information, awareness, and availability of COVID-19 vaccines are key challenges. Somalia launched the COVID-19 vaccination in March 2021; however, the uptake of the vaccination is slow, which creates fear of further loss of life in the country unless intentional and organized campaigning and efforts are made to improve both the availability of the vaccine and its acceptance by the community. This study aimed to understand the current level of awareness, accessibility, trust, and hesitancy toward the COVID-19 vaccine among women in Somalia. Methods: To assess COVID-19 vaccine uptake, acceptance, community awareness, and hesitancy rates in Somalia, we carried out a cross-sectional mixed methods study in three regions of Somalia that were selected randomly out of the 18 regions of Somalia. A multi-theory model (MTM) was developed to identify correlated factors associated with the hesitancy or non-hesitancy toward COVID-19 vaccination among women of all ages (18 years and above). Results: A total of 999 eligible women (333 in each district) of 18–98 years old were interviewed in March 2022. About two-thirds (63.76%) of participants reported hesitancy about receiving the COVID-19 vaccine. The theory model initiation construct indicated that behavioral confidence in the vaccine (b = 0.476, p < 0.001), participatory dialogue (at b = 0.136, p < 0.004), and changes in the physical environment (b = 0.248, p = 0.015) were significantly associated with COVID-19 vaccine acceptance among women who were not hesitant to take the vaccine. Conclusions: The availability of COVID-19 vaccines may not translate into their uptake. The decision to get the vaccine was determined by multiple factors, including the perceived value of the vaccination, previous experience with the vaccine, perceived risk of infection, accessibility and affordability, and trust in the vaccine itself. Public health education programming and messaging must be developed to encourage vaccine uptake among women with varying levels of vaccine hesitancy. Full article

The rising issues of herpes simplex virus (HSV)-2 drug ramifications have encouraged the researchers to look for new and alternative approaches that pose minimum adversities in the host while efficiently reducing the HSV-2 infection. Although microRNAs (miRNAs), as unorthodox approaches, are gaining popularity due to eliciting highly reduced immunogenic reactions, their implications in HSV-2 research have been rarely explored. In this study, a pool of cellular miRNAs with significance in HSV-2-induced inflammatory and immune responses have been identified. Computationally recognizing the host targets of these miRNAs through network biology and machine learning, in vitro validation has been addressed along with the identification of their regulation in the HSV-2 infection. To signify the role of these identified miRNAs, they have been individually ectopically expressed in macrophages. The ectopic expression of the individual miRNAs was able to suppress HSV-2 viral gene expression. Taking a step forward, this study also highlights the Box–Behnken design-based combinatorial effect of ectopically expressed miRNAs on maximum suppression of HSV-2 infectivity. Therefore, the concentrations of each of the miRNAs optimized in a combination, predicted through expert systems biology tools were validated in vitro to not only recover the target expressions but also inhibit the HSV-2 infection in the macrophages. Overall, the study offers miRNAs as intriguing alternatives to commercially available medications against HSV-2. Moreover, the study illuminates the prophylactic potentiality of the miRNAs, which is significant since there are currently no vaccines available for HSV-2. Moving forward, the miRNAs are employed in an innovative strategy that incorporates intricate biological system models and in vitro confirmation methods to deliver a prospective combinatorial miRNA therapeutic against HSV-2 infection. Full article

Foot-and-mouth disease (FMD) is a fatal contagious viral disease that affects cloven-hoofed animals and causes severe economic damage at the national level. There are seven serotypes of the causative foot-and-mouth disease virus (FMDV), and type O is responsible for serious outbreaks and shows a high incidence. Recently, the Cathay, Southeast Asia (SEA), and ME-SA (Middle East-South Asia) topotypes of type O have been found to frequently occur in Asia. Thus, it is necessary to develop candidate vaccines that afford protection against these three different topotypes. In this study, an experimental FMD vaccine was produced using a recombinant virus (TWN-JC) with the JC epitope (VP1 140–160 sequence of the O/SKR/Jincheon/2014) between amino acid 152 and 153 of VP1 in TWN-R. Immunization with this novel vaccine candidate was found to effectively protect mice against challenge with the three different topotype viruses. Neutralizing antibody titers were considerably higher after a second vaccination. The serological differences between the topotype strains were identified in guinea pigs and swine. In conclusion, a significant serological difference was observed at 56 days post-vaccination between animals that received the TWN-JC vaccine candidate and those that received the positive control virus (TWN-R). The TWN-JC vaccine candidate induced IFNγ and IL-12B. Full article

In 2006, the human papillomavirus (HPV) vaccine was approved for use as an effective intervention for reducing the risk of developing cervical cancer; however, its successful implementation is dependent on acceptability. This study aims to provide a comprehensive understanding of the reasons that favor or do not favor the acceptability of HPV vaccines. Methods: We conducted a systematic review and meta-summary of qualitative research on 16 databases. A total of 32 articles that considered the perspectives of vaccine users, their parents, and the professionals who care for them were reviewed. Synthesis was conducted as described by Sandelowski and Barroso. Results: We used inductive and deductive methods to obtain a total of 22 dimensions, out of which three issues stood out that should be considered to improve acceptability and are formed by three groups of study, namely, information about the vaccine, fears and side effects, and sexuality associated with the vaccine. Conclusions: Acceptability, as well as adherence to HPV vaccination, is a complex concept. This review highlights the perspectives of the three sets of actors involved in the process (i.e., users, parents, and professionals) and views these factors in relation to acceptability as a guide for new interventions. Full article

CD4⁺ T cells have been found to play critical roles in the control of both acute and chronic Toxoplasma infection. Previous studies identified a protective role for the Toxoplasma CD4⁺ T cell-eliciting peptide AS15 (AVEIHRPVPGTAPPS) in C57BL/6J mice. Herein, we found that immunizing mice with AS15 combined with GLA-SE, a TLR-4 agonist in emulsion adjuvant, can be either helpful in protecting male and female mice at early stages against Type I and Type II Toxoplasma parasites or harmful (lethal with intestinal, hepatic, and spleen pathology associated with a storm of IL6). Introducing the universal CD4⁺ T cell epitope PADRE abrogates the harmful phenotype of AS15. Our findings demonstrate quantitative and qualitative features of an effective Toxoplasma-specific CD4⁺ T cell response that should be considered in testing next-generation vaccines against toxoplasmosis. Our results also are cautionary that individual vaccine constituents can cause severe harm depending on the company they keep. Full article

Background: Human respiratory syncytial virus (hRSV) is a key contributor to lower respiratory tract infections (LRTIs), affecting children aged 0–5 years and often leading to outpatient visits, emergency department utilization, and hospitalization. With the development of hRSV vaccines for mitigation, understanding the epidemiological impact of hRSV infections among 0–5-year-old pediatric outpatients in Italy is crucial. Methods: This systematic review conducted searches on PubMed, Embase, Scopus, and the International HTA Database, yielding 20,845 English and Italian records from January 2000 to July 2022. Results: Six eligible articles were identified following inclusion and exclusion criteria. These studies demonstrated hRSV-positivity proportions ranging from 18% to 41% in pediatric outpatients with respiratory infections. However, data comparability was hindered by diverse diagnostic approaches, data sources, sample populations, and study designs. Notably, hRSV-positivity showed temporal variability, rising from 23.8% (2001–2002) to 40.6% (2019–2020). This trend could stem from evolving epidemiological factors, heightened clinician awareness in hRSV diagnosis, or more sensitive molecular techniques. Conclusion: As the first review of its kind, this study underscores the need for more comprehensive data to inform effective preventive strategies against hRSV-related burdens in pediatric outpatients. Full article

Porcine Circovirus type 2 (PCV2) vaccination of gilts during acclimation has become a routine practice in commercial pig farms to homogenize herd immunity to PCV2 and reduce the impact of diseases associated with PCV2 infection, namely reproductive, respiratory, systemic, and other PCV2-associated diseases. The periodic mass vaccination of sows, with the same objectives, is also common. To ensure mass vaccination is an appropriate health management tool, demonstrating that the vaccine is safe in different sow/gilt physiological stages is necessary. The objective of the present studies was to evaluate safety of a PCV2a/PCV2b/Mycoplasma hyopneumoniae (PCV2a2bMHP) killed vaccine in sows and gilts during gestation and lactation, under controlled experimental pen conditions, and during gestation, mimicking mass vaccination, under field conditions. Safety was assessed by monitoring for immediate adverse reactions after vaccination, rectal temperatures after vaccination (controlled experimental pen studies only), local and systemic reactions, and reproductive performance (studies conducted during pregnancy) or lactation performance (studies conducted during lactation). In total, 416 sows/gilts were enrolled, and more than 4000 piglets were observed during their first week of life, under field conditions. In both controlled experimental and field studies, no immediate anaphylactic type reactions were observed after vaccination and the incidence of adverse events, such as depression or decreased appetite, was acceptable for what is expected in a swine herd. In the studies conducted during gestation, vaccination did not significantly increase rectal temperature of the vaccinated animals. Sow reproductive outcomes were not affected by vaccination. The farrowing rate of animals participating in the field study was higher than the historic averages of the farms. In the laboratory studies conducted during the first and second half of gestation, no differences in reproductive outcome were observed between vaccinated and non-vaccinated animals. However, sows vaccinated during lactation experienced a transient hyperthermia which did not affect milk production since the piglets’ average daily weight gain was not affected. The previously described results confirm that the administration of a PCV2a2bMHP vaccine was safe in the tested conditions. All the anticipated benefits of sow and gilt PCV2 vaccination, such as homogenization of PCV2 antibody titers or reduction in PCV2 circulation in the herd, would not be masked by potential adverse events due to herd vaccination. In conclusion, the administration of a PCV2a2bMHP vaccine to sows and gilts during different stages of gestation and during lactation is safe. Full article

Respiratory syncytial virus (RSV) is the most common pathogen causing respiratory tract infections in infants, affecting over 90% of children within the first two years of life. It may cause lower respiratory tract infections, which constitute a significant healthcare burden both in the primary and secondary care settings. Meanwhile, the data regarding RSV disease in Poland is scarce, and published data significantly differs from the numbers reported for other countries with longstanding surveillance and reporting systems. A literature review and an expert panel were conducted to (1) understand the healthcare burden of RSV infections in Poland; (2) collect data on infection seasonality, patient pathway, and management patterns; and (3) evaluate RSV infection surveillance in Poland. According to the literature, RSV is the major agent responsible for non-influenza respiratory diseases in Poland. The reported rates of hospitalization for RSV infections are 267.5/100,000 for children under 5 years of age and 1132.1/100,000 for those under 1 year of age. Comparisons with data from other countries suggest that these values may be underestimated, possibly due to insufficient access to microbiological testing and a low awareness of RSV. Infections occur mainly between December and April, however, this pattern has changed following the implementation of preventive measures for coronavirus disease 2019 in the past few years. According to available reports, bronchodilators, antibiotics, corticosteroids, and X-ray imaging have been frequently used. The surveillance system in Poland has limitations, but these may be overcome due to recent changes in healthcare law as well as the availability and reimbursement of diagnostic tests. Full article

Messenger RNA (mRNA) vaccines belong to a new class of medications, RNA therapeutics, including both coding and non-coding RNAs. The use of mRNA as a therapy is based on the biological role of mRNA itself, namely its translation into a functional protein. The goal of mRNA vaccines is to produce a specific antigen in cells to elicit an immune response that might be prophylactic or therapeutic. The potential of mRNA as vaccine has been envisaged for years but its efficacy has been clearly demonstrated with the approval of COVID-19 vaccines in 2021. Since then, mRNA vaccines have been in the pipeline for diseases that are still untreatable. There are many advantages of mRNA vaccines over traditional vaccines, including easy and cost-effective production, high safety, and high-level antigen expression. However, the nature of mRNA itself and some technical issues pose challenges associated with the vaccines’ development and use. Here we review the immunological and pharmacological features of mRNA vaccines by discussing their pharmacokinetics, mechanisms of action, and safety, with a particular attention on the advantages and challenges related to their administration. Furthermore, we present an overview of the areas of application and the clinical trials that utilize a mRNA vaccine as a treatment. Full article