Vaccines, Volume 12, Issue 5 (May 2024) – 94 articles

The development of a safe and effective vaccine against avian influenza A virus (AIV) H5N8 is relevant due to the widespread distribution of this virus in the bird population and the existing potential risk of human infection, which can lead to significant public health concerns. Here, we developed an experimental pVAX-H5 DNA vaccine encoding a modified trimer of AIV H5N8 hemagglutinin. Immunization of BALB/c mice with pVAX-H5 using jet injection elicited high titer antibody response (the average titer in ELISA was 1 × 10⁵), and generated a high level of neutralizing antibodies against H5N8 and T-cell response, as determined by ELISpot analysis. Both liquid and lyophilized forms of pVAX-H5 DNA vaccine provided 100% protection of immunized mice against lethal challenge with influenza A virus A/turkey/Stavropol/320-01/2020 (H5N8). The results obtained indicate that pVAX-H5 has good opportunities as a vaccine candidate against the influenza A virus (H5N8). Full article

A universal vaccine that generally prevents influenza virus infection and/or illness remains elusive. We have been exploring a novel approach to vaccination involving replication-competent controlled herpesviruses (RCCVs) that can be deliberately activated to replicate efficiently but only transiently in an administration site in the skin of a subject. The RCCVs are derived from a virulent wild-type herpesvirus strain that has been engineered to contain a heat shock promoter-based gene switch that controls the expression of, typically, two replication-essential viral genes. Additional safety against inadvertent replication is provided by an appropriate secondary mechanism. Our first-generation RCCVs can be activated at the administration site by a mild local heat treatment in the presence of an antiprogestin. Here, we report that epidermal vaccination with such RCCVs expressing a hemagglutinin or neuraminidase of an H1N1 influenza virus strain protected mice against lethal challenges by H1N1 virus strains representing 75 years of evolution. Moreover, immunization with an RCCV expressing a subtype H1 hemagglutinin afforded full protection against a lethal challenge by an H3N2 influenza strain, and an RCCV expressing a subtype H3 hemagglutinin protected against a lethal challenge by an H1N1 strain. Vaccinated animals continued to gain weight normally after the challenge. Protective effects were even observed in a lethal influenza B virus challenge. The RCCV-based vaccines induced robust titers of in-group, cross-group and even cross-type neutralizing antibodies. Passive immunization suggested that observed vaccine effects were at least partially antibody-mediated. In summary, RCCVs expressing a hemagglutinin induce robust and very broad cross-protective immunity against influenza. Full article

Importance: Hepatitis B is a serious problem in the United States (US), with up to 2.4 million Americans living with a chronic infection. Only 26–32% of people living with hepatitis B in the US are diagnosed. Additionally, just 30% of all adults are vaccinated against the virus. In 2022, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) updated adult hepatitis B vaccination recommendations to include all adults aged 19–59 years and those 60 years and older with risk factors for hepatitis B. Subsequently, in 2023, the CDC recommended that all adults be screened at least one time in their lives. Observations: Electronic health record (EHR) tools (prompts, order sets, etc.) have proven to be an effective method of increasing hepatitis B screening and vaccination, but longstanding challenges and questions around hepatitis B vaccines and tests could prevent effectual EHR implementation. As the new recommendations directly impact providers who may have limited familiarity with hepatitis B, guidance on how to identify eligible patients and triggers, order sets to facilitate vaccine/test selection, and proper documentation and patient follow-up is necessary. Conclusions and Relevance: This communication offers a practical framework for health systems to build an effective EHR strategy for the updated adult hepatitis B recommendations. We also provide comprehensive responses to clinicians’ questions that are frequently asked prior to screening or vaccinating for hepatitis B. Full article

MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4⁺ T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains. Full article

Objective: To evaluate the preference of primary HCWs and residents on vaccination consultation in community health services to provide evidence for vaccine hesitancy intervention strategies. Methods: A discrete choice model (DCM) was constructed to evaluate the preference difference between primary HCWs and residents on vaccination consultation in community health services in China during May–July 2022. Results: A total of 282 residents and 204 HCWs were enrolled in this study. The residents preferred consulting with an HCW-led approach (β = 2.168), with specialized content (β = 0.954), and accompanied by telephone follow-up (β = 1.552). In contrast, the HCWs preferred face-to-face consultation (β = 0.540) with an HCW-led approach (β = 0.458) and specialized content (β = 0.409), accompanied by telephone follow-up (β = 0.831). College residents and residents with underlying self-reported disease may be near-critically inclined to choose traditional consultation (an offline, face-to-face consultation with standardized content and more prolonged duration) rather than a new-media consulting group (an online consultation with specialized content within 5 min). Urban HCWs preferred long-term consultation groups (the resident-led offline consultation with follow-up lasting more than 5 min). In contrast, rural HCWs preferred efficient consultation (the HCW-led, short-duration, standardized offline consultation mode). Conclusion: The selection preference for vaccine consultation reveals a gap between providers and demanders, with different groups exhibiting distinct preferences. Identifying these targeted gaps can help design more acceptable and efficient interventions, increasing their likelihood of success and leading to better resource allocation for policymakers to develop targeted vaccination policies. Full article

Merkel cell carcinoma is a rare, aggressive skin cancer that mainly occurs in elderly and immunocompromised patients. Due to the success of immune checkpoint inhibition in MCC, the importance of immunotherapy and vaccines in MCC has increased in recent years. In this article, we aim to present the current progress and perspectives in the development of vaccines for this disease. Here, we summarize and discuss the current literature and ongoing clinical trials investigating vaccines against MCC. We identified 10 articles through a PubMed search investigating a vaccine against MCC. From the international clinical trial database Clinical.Trials.gov, we identified nine studies on vaccines for the management of MCC, of which seven are actively recruiting. Most of the identified studies investigating a vaccine against MCC are preclinical or phase 1/2 trials. The vaccine principles mainly included DNA- and (synthetic) peptide-based vaccines, but RNA-based vaccines, oncolytic viruses, and the combination of vaccines and immunotherapy are also under investigation for the treatment of MCC. Although the management of MCC is changing, when compared to times before the approval of immune checkpoint inhibitors, it will still take some time before the first MCC vaccine is ready for approval. Full article

This paper simulates a hypothetical pan-coronavirus vaccine that confers immediate sterilizing immunity against all SARS-CoV-2 variants. Simulations used a SEIIS (susceptible, exposed, infective, immune, susceptible) spreadsheet model that ran two parallel subpopulations: one that accepted vaccination and another that refused it. The two subpopulations could transmit infections to one another. Using data from the United States (US), the simulated vaccine was tested against limiting factors such as vaccine hesitancy, slow vaccination distribution, and the development of high-transmission variants. The vaccine was often successful at reducing cases, but high-transmission variants and discontinuation of non-pharmaceutical interventions (NPIs) such as masking greatly elevated cases. A puzzling outcome was that if NPIs were discontinued and high-transmission variants became common, the model predicted consistently higher rates of disease than are actually observed in the US in 2024. However, if cumulative exposure to virus antigens increased the duration of immunity or decreased the infectivity of the virus, the model predictions were brought back into a more realistic range. The major finding was that even when a COVID-19 vaccine always produces sterilizing immunity against every SARS-CoV-2 variant, its ability to control the epidemic can be compromised by multiple common conditions. Full article

MF59 and AS03 are squalene emulsion-based vaccine adjuvants with similar compositions and droplet sizes. Despite their broad use in licensed influenza vaccines, few studies compared their adjuvant effects and action mechanisms side by side. Considering the majority of adjuvants act on dendritic cells (DCs) to achieve their adjuvant effects, this study compared MF59 and AS03-like adjuvants (AddaVax and AddaS03, respectively) to enhance antigen uptake, DC maturation, ovalbumin (OVA) and seasonal influenza vaccine-induced immune responses. Considering MF59 was reported to activate MyD88 to mediate its adjuvant effects, this study also investigated whether the above-explored adjuvant effects of AddaVax and AddaS03 depended on MyD88. We found AddaVax more potently enhanced antigen uptake at the local injection site, while AddaS03 more potently enhanced antigen uptake in the draining lymph nodes. AddaS03 but not AddaVax stimulated DC maturation. Adjuvant-enhanced antigen uptake was MyD88 independent, while AddaS03-induced DC maturation was MyD88 dependent. AddaVax and AddaS03 similarly enhanced OVA-induced IgG and subtype IgG1 antibody responses as well as influenza vaccine-induced hemagglutination inhibition antibody titers, whileAddaS03 more potently enhanced OVA-specific IgG2c antibody responses. Both adjuvants depended on MyD88 to enhance vaccine-induced antibody responses, while AddaVax depended more on MyD88 to achieve its adjuvant effects. Our study reveals similarities and differences of the two squalene emulsion-based vaccine adjuvants, contributing to our improved understanding of their action mechanisms. Full article

Tuberculosis (TB), a chronic infectious disease affecting humans, causes over 1.3 million deaths per year throughout the world. The current preventive vaccine BCG provides protection against childhood TB, but it fails to protect against pulmonary TB. Multiple candidates have been evaluated to either replace or boost the efficacy of the BCG vaccine, including subunit protein, DNA, virus vector-based vaccines, etc., most of which provide only short-term immunity. Several live attenuated vaccines derived from Mycobacterium tuberculosis (Mtb) and BCG have also been developed to induce long-term immunity. Since Mtb mediates its virulence through multiple secreted proteins, these proteins have been targeted to produce attenuated but immunogenic vaccines. In this review, we discuss the characteristics and prospects of live attenuated vaccines generated by targeting the disruption of the genes encoding secretory mycobacterial proteins. Full article

Since 2018, Taiwan has included the human papillomavirus (HPV) vaccination into its national immunization program for junior high school girls. However, the reports of side effects following vaccination have increased parental concerns. This study investigated parental intentions regarding the HPV vaccination for their daughters and related factors in Taiwan. A total of 213 parents of girls aged between 12 and 15 years participated in an online survey. The survey collected data on various factors, including the parental intention to vaccinate their daughters against HPV; the motivation behind the vaccinations, as measured using the Motors of Human Papillomavirus Vaccination Acceptance Scale; an understanding of the reasons behind the government’s promotion of HPV vaccinations; concerns regarding the side effects of vaccinations for their daughters; an awareness of the reported side effects of HPV vaccines experienced by some individuals; the exposure to information on HPV vaccines from social media; and mental health status, measured using the Brief Symptom Rating Scale. The associations between these variables and the parental intention to vaccinate their daughters against HPV were examined using a multivariable linear regression analysis model. The findings revealed a moderate to high level of intention among participants to vaccinate their daughters against HPV. Parents who perceived a greater value in HPV vaccination for their daughters’ health (B = 0.524, standard error [se] = 0.039, p < 0.001) and had greater autonomy in decision-making regarding vaccination (B = 0.086, se = 0.038, p = 0.026) exhibited a higher intention to vaccinate their daughters against HPV. Conversely, parents who expressed greater concern regarding the side effects of HPV vaccines for their daughters had a lower intention to vaccinate (B = −0.762, se = 0.203, p < 0.001). Based on these findings, this study recommends integrating these factors into the design of intervention programs aimed at enhancing parental intentions to vaccinate their daughters against HPV. Full article

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods often utilised for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical, and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products, and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups so that they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission has many potential benefits. These include: reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review. Full article

Background: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01_B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, as a proxy of clinical effectiveness. Methods: This systematic review examined post-vaccination parameters: humoral and cell-mediated immunity, avidity index, geometric mean concentration of antibody (GMC), and immunity persistence. The meta-analysis used a random-effects model, and subgroup and meta-regression analyses were conducted. Results: Among 37 included articles, after one month from RZV-dose 2, the pooled response rate for anti-gE humoral immunity was 95.2% (95%CI 91.9–97.2), dropping to 77.6% (95%CI 64.7–86.8) during immunosuppression. The anti-gE cell-mediated immunity-specific response reached 84.6% (95%CI 75.2–90.9). Varying factors, such as age, sex, coadministration with other vaccines, prior HZ, or live-attenuated zoster vaccine, did not significantly affect response rates. RZV induced a substantial increase in gE avidity. Immunity persistence was confirmed, with more rapid waning in the very elderly. Conclusions: This systematic review indicates that RZV elicits robust immunogenicity and overcomes immunocompromising conditions. The findings underscore the need for further research, particularly on long-term immunity, and have the potential to support HZ vaccination policies and programs. Full article

The COVID-19 vaccine is safe and effective for children, yet parental hesitancy towards vaccinating children against the virus persists. We conducted a telephone-administered weighted survey in Texas to examine parents’ sociodemographic factors and medical conditions associated with COVID-19 vaccination intention for parents with unvaccinated children ages 5–17 years. We collected responses from 19,502 participants, of which 4879 were parents of children ages 5–17 years. We conducted multiple logistic regression with Lasso-selected variables to identify factors associated with children’s vaccination status and parents’ intention to vaccinate their children. From the unweighted sample, less than half of the parents (46.8%) had at least one unvaccinated child. These parents were more likely to be White, English-speaking, not concerned about illness, privately insured, and unvaccinated for COVID-19 themselves (p < 0.001). In the adjusted regression model, parents who were unvaccinated (vs. having COVID-19 booster, aOR = 28.6) and financially insecure (aOR = 1.46) had higher odds of having unvaccinated children. Parents who were Asian (aOR = 0.50), Black (aOR = 0.69), Spanish-speaking (aOR = 0.57), concerned about illness (aOR = 0.63), had heart disease (aOR = 0.41), and diabetes (aOR = 0.61) had lower odds of having unvaccinated children. Parents who were Asian, Black, Hispanic, Spanish-speaking, concerned about illness for others, and vaccine-boosted were more likely to have vaccination intention for their children (p < 0.001). Children’s vaccination is essential to reduce COVID-19 transmission. It is important to raise awareness about the value of pediatric COVID-19 vaccination while considering parents’ sociodemographic and medical circumstances. Full article

Pertussis continues to be a significant public health concern. We aimed to examine the epidemiological characteristics of pertussis in Vojvodina, which accounts for almost a third of Serbia’s population. Our aim was to determine the overall and age-specific incidence and mortality rates of pertussis in Vojvodina from 1948 to 2023, as well as the coverage of immunization against pertussis from 1960 to 2023. In the period 1948–2023, 42,259 cases of pertussis were reported. Following the introduction of the DTwP vaccine (1960) in Serbia, the reported incidence of pertussis began to decline. In 2001, for the first time since introduction of pertussis surveillance in Vojvodina, no pertussis cases were reported. Since 2012, the reported incidence of pertussis has once again increased, and peaked (41.1/100,000) in 2023, approaching the incidence rates recorded shortly after the introduction of DTwP vaccine. A shift in the age profile of pertussis from children aged 0–6 years to school-aged children (7–14 years) occurred between 2012 and 2023, when 48.3% of pertussis cases occurred in this age group. Although the incidence rates of pertussis among individuals aged 20 years and older were significantly lower than among younger age groups, there is evidence of an increasing trend in pertussis cases, particularly among those aged 40–49 years, since 2012. Based on the findings of this study, it is imperative to introduce additional booster doses of the aP vaccine for individuals aged 14 years, along with implementing maternal immunization strategies targeting women of childbearing age. Full article

Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including tuberculosis and COVID-19. Cost-effective and scalable biomanufacturing processes are critical for the commercialization of adenovirus-vectored vaccines. Adenoviral vectors are commonly produced through the infection of batch cultures at low cell density cultures, mostly because infections at high cell densities result in reduced cell-specific virus productivity and does not improve volumetric productivity. In this study, we have investigated the feasibility of improving the volumetric productivity by infecting fed-batch cultures at high cell densities. Four commercial and one in-house developed serum-free media were first tested for supporting growth of HEK 293 cells and production of adenovirus type 5 (Ad5) in batch culture. Two best media were then selected for development of fed-batch culture to improve cell growth and virus productivity. A maximum viable cell density up to 16 × 10⁶ cells/mL was achieved in shake flask fed-batch cultures using the selected media and commercial or in-house developed feeds. The volumetric virus productivity was improved by up to six folds, reaching 3.0 × 10¹⁰ total viral particles/mL in the fed-batch culture cultivated with the media and feeds developed in house and infected at a cell density of 5 × 10⁶ cells/mL. Additional rounds of optimization of media and feed were required to maintain the improved titer when the fed-batch culture was scaled up in a bench scale (3 L) bioreactor. Overall, the results suggested that fed-batch culture is a simple and feasible process to significantly improve the volumetric productivity of Ad5 through optimization and balance of nutrients in culture media and feeds. Full article

Influenza vaccination is an important public health measure that can reduce disease burden, especially among older persons (those aged 65 and over) who have weaker immune systems. Evidence suggests enhanced vaccines, including adjuvanted quadrivalent vaccines (aQIV), may be particularly effective in this group. This study reports the results of a systematic review of the cost-effectiveness of aQIV in this population. The review was undertaken and reported in accordance with good practice guidelines. Medline and EMBASE were searched from 2013 to the present. Pre-selected eligibility criteria were employed and quality assessment undertaken using the Consensus Health Economic Criteria (CHEC-extended) checklist and Consolidated Health Economic Evaluation Reporting Standard (CHEERS) 2022 checklists. A total of 124 records were returned, with 10 full text papers retained. All were modelling studies and exhibited heterogeneity in approach, perspective, and parameter estimation. Nine papers reported cost-effectiveness ranging from EUR 6694/QALY to EUR 20,000/QALY in evaluations employing a payer perspective and from EUR 3936/QALY to EUR 17,200/QALY in those using a societal perspective. Results remained robust to a range of sensitivity analyses. One paper that reported contrary findings adopted a distinct modelling approach. It is reasonable to conclude that there is a broad consensus as to the cost-effectiveness of aQIV in this population group. Full article

Highly contagious diseases, such as mumps, are a global concern as new epidemics continue to emerge, even in highly vaccinated populations. The risk of transmission and spread of these viruses is even higher for individuals who are more likely to be exposed, including healthcare workers (HCWs). In healthcare settings, both HCWs and patients are at risk of infection during the care process, potentially leading to nosocomial epidemic outbreaks. Mumps is often underestimated compared with measles and rubella, despite being milder and less likely to spread. In fact, the risk of complications following mumps infection is extremely high, especially if the disease occurs in adulthood. The measles–mumps–rubella (MMR) vaccine has been shown to be an excellent preventive measure. Unfortunately, the mumps component appears to be less effective in inducing immunity than those for measles and rubella (two-dose effectiveness of 85%, 95% and 97%, respectively). The main aim of our study was to investigate the prevalence of detectable mumps antibodies (serum IgG antibodies) in a cohort of Italian and foreign HCWs in relation to personal and occupational factors. We included in the study 468 subjects who underwent health surveillance at the Occupational Medicine Unit of the Tor Vergata Polyclinic in Rome during the period from January 2021 to March 2023. In our study, the proportion of HCWs found to be unprotected against mumps was very high (8.3%), and those found to be immune are below the WHO threshold for herd immunity (95%). From our data, it seems essential that all occupational health services carry out an accurate screening with a dose of anti-mumps antibodies to assess serological protection before starting a job, regardless of an individual’s vaccination history. This approach is proving to be beneficial, accurate, as it allows all serologically non-immune individuals to be vaccinated in the workplace, including those who would be protected by their vaccination history but have lost the antibody response. Full article

State-level COVID-19 vaccination rates among older adults have been uneven in the United States. Due to the immunocompromised nature of older adults, vaccine hesitancy increases the risk of morbidity and mortality. This study aims to determine the association between the social determinants of health, the structural determinants of health, and COVID-19 vaccine hesitancy among older adults in the United States. Secondary data from the Health and Retirement Study (HRS) dataset were used. A descriptive analysis and multinomial multivariable logistic regression were performed to examine the association of the independent variables—gender, age, race, immigration status, marital status, broadband internet access, social security income, Medicare coverage, education, and frequency of religious service—with the dependent variable, vaccine hesitancy. Compared to the respondents with no vaccine hesitancy and without the specific predictor, the respondents who reported religious attendance at least once/week were more likely to be “somewhat hesitant”, divorced respondents had higher odds of being “somewhat hesitant”, and older adults aged 65–74 years were more likely to be “very hesitant” or “somewhat hesitant” about the COVID-19 vaccine. Compared to the respondents with no vaccine hesitancy and without the specific predictor, females had higher odds of being “very hesitant”, “somewhat hesitant”, or a “little hesitant”, and African Americans were more likely to be “very hesitant”, “somewhat hesitant”, or a “little hesitant” about the COVID-19 vaccine. Addressing these factors may limit the barriers to vaccine uptake reported among older adults and improve herd immunity among the immunocompromised population. Full article

People with HIV (PWH) frequently suffer from Opioid (OP) Use Disorder (OUD). In an investigation of the impact of OUD on underlying immune dysfunction in PWH, we previously reported that OP use exacerbates inflammation in virally controlled PWH followed in the Infectious Diseases Elimination Act (IDEA) Syringe Services Program (SSP). Unexpectedly, Flu vaccination-induced antibody responses in groups with OUD were superior to PWH without OUD. Here, we investigated the profile of 48 plasma biomarkers comprised of TNF and Ig superfamily (SF) molecules known to impact interactions between T and B cells in 209 participants divided into four groups: (1) HIV+OP+, (2) HIV−OP+, (3) HIV+OP−, and (4) HIV−OP−. The differential expression of the top eight molecules ranked by median values in individual Groups 1–3 in comparison to Group 4 was highly significant. Both OP+ groups 1 and 2 had higher co-stimulatory TNF SF molecules, including 4-1BB, OX-40, CD40, CD30, and 4-1BBL, which were found to positively correlate with Flu Ab titers. In contrast, HIV+OP− exhibited a profile dominant in Ig SF molecules, including PDL-2, CTLA-4, and Perforin, with PDL-2 showing a negative correlation with Flu vaccine titers. These findings are relevant to vaccine development in the fields of HIV and OUD. Full article

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

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs. Full article

African swine fever (ASF) is a deadly disease of swine currently causing a worldwide pandemic, leading to severe economic consequences for the porcine industry. The control of disease spread is hampered by the limitation of available effective vaccines. Live attenuated vaccines (LAVs) are currently the most advanced vaccine prototypes, providing strong protection against ASF. However, the significant advances achieved using LAVs must be complemented with further studies to analyze vaccine-induced immunity. Here, we characterized the onset of cross-protective immunity triggered by the LAV candidate BA71ΔCD2. Intranasally vaccinated pigs were challenged with the virulent Georgia 2007/1 strain at days 3, 7 and 12 postvaccination. Only the animals vaccinated 12 days before the challenge had effectively controlled infection progression, showing low virus loads, minor clinical signs and a lack of the unbalanced inflammatory response characteristic of severe disease. Contrarily, the animals vaccinated 3 or 7 days before the challenge just showed a minor delay in disease progression. An analysis of the humoral response and whole blood transcriptome signatures demonstrated that the control of infection was associated with the presence of virus-specific IgG and a cytotoxic response before the challenge. These results contribute to our understanding of protective immunity induced by LAV-based vaccines, encouraging their use in emergency responses in ASF-affected areas. Full article

SARS-CoV-2 vaccination-induced protection against infection is likely to be affected by functional antibody features. To understand the kinetics of antibody responses in healthy individuals after primary series and third vaccine doses, sera from the recipients of the two licensed SARS-CoV-2 mRNA vaccines were assessed for circulating anti-SARS-CoV-2 spike IgG levels and avidity for up to 6 months post-primary series and 9 months after the third dose. Following primary series vaccination, anti-SARS-CoV-2 spike IgG levels declined from months 1 to 6, while avidity increased through month 6, irrespective of the vaccine received. The third dose of either vaccine increased anti-SARS-CoV-2 spike IgG levels and avidity and appeared to enhance antibody level persistence—generating a slower rate of decline in the 3 months following the third dose compared to the decline seen after the primary series alone. The third dose of both vaccines induced significant avidity increases 1 month after vaccination compared to the avidity response 6 months post-primary series vaccination (p ≤ 0.001). A significant difference in avidity responses between the two vaccines was observed 6 months post-third dose, where the BNT162b2 recipients had higher antibody avidity levels compared to the mRNA-1273 recipients (p = 0.020). Full article

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

Coronavirus disease 2019 (COVID-19) is a highly contagious zoonotic respiratory disease with many similarities to influenza. Effective vaccines are available for both; however, rapid viral evolution and waning immunity make them virtually impossible to eradicate with vaccines. Thus, the practical goal of vaccination is to reduce the incidence of serious illnesses and death. Three years after the introduction of COVID-19 vaccines, the optimal vaccination strategy in the endemic period remains elusive, and health authorities worldwide have begun to adopt various approaches. Herein, we propose a COVID-19 vaccination strategy based on the data available until early 2024 and discuss aspects that require further clarification for better decision making. Drawing from comparisons between COVID-19 and influenza vaccination strategies, our proposed COVID-19 vaccination strategy prioritizes high-risk groups, emphasizes seasonal administration aligned with influenza vaccination campaigns, and advocates the co-administration with influenza vaccines to increase coverage. Full article

This is a cross-sectional serosurveillance study for RSV. Between June and September of 2021, a total of 150 sera were collected from 30 individuals in each age group (<5, 5–18, 19–49, 50–64, and ≥65 years). Seroprevalence was estimated using enzyme-linked immunosorbent assays targeting two stabilized prefusion F (preF; DS-Cav1 and SC-TM) and G proteins. The overall seroprevalence was low in young children and older adults, despite them having a higher risk of severe RSV infection. There was a remarkable difference in age-stratified seroprevalence rates between anti-preF and anti-G protein antibodies. Given the high disease burden and low seroprevalence in both infants and old adults, RSV vaccination would be crucial for pregnant women and people aged over 60 years. Full article

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

We developed and tested MivacunaLA/MyshotLA, a community-informed mobile phone intervention, to increase COVID-19 vaccination among Latino parents/caretakers of minors in under-resourced areas of Los Angeles by addressing misinformation and building trust. We recruited Latino parents/caregivers with at least one unvaccinated child in East and South Los Angeles in the summer of 2021 and evaluated MivacunaLA as a randomized controlled trial with a wait-list control group. A difference-in-difference analysis showed Latino parents/caregivers that participated in MivacunaLA (n = 246), in comparison to the control group, were 15 percentage points more likely (p = 0.04) to report vaccination of minors aged 12–17 years, and 12 percentage points more likely (p = 0.03) to report a positive intention to vaccinate minors aged 2–11 years (when COVID-19 vaccines became available). Mobile phone-delivered digital interventions using videos and culturally tailored educational material to promote COVID-19 vaccine confidence can be an effective way to combat misinformation and deliver timely information to marginalized communities. Community-based participatory research approaches are crucial to advance health equity among minority communities, especially immigrant Spanish-speaking underserved communities. Full article

Despite clear evidence of the public health benefits of the human papillomavirus (HPV) vaccine in preventing HPV-related cancers and genital warts, underutilization of HPV vaccination in the United States persists. Interventions targeting multi-level determinants of vaccination behavior are crucial for improving HPV vaccination rates. The study’s purpose was to implement and evaluate the adapted Adolescent Vaccination Program (AVP), a clinic-based, multi-level, multi-component intervention aimed at increasing HPV vaccine initiation and completion rates in a five-clinic pediatric network in Bexar County, Texas. The adaptation process was guided by established frameworks and involved formative work with clinic stakeholders. The study utilized a quasi-experimental single group pre- and post- study design, with an external comparison data using the National Immunization Survey-Teen (NIS-Teen) datasets for the same time period to examine the AVP’s effect on HPV vaccination initiation and completion. A series of interrupted time series analyses (ITSA) compared the clinic system patient outcomes (HPV vaccination initiation and completion rates) in the post-intervention to the general adolescent population (NIS-Teen). Of the 6438 patients (11–17 years) with clinic visits during the 3-year study period, HPV vaccination initiation rates increased from 64.7% to 80.2% (p < 0.05) and completion rates increased from 43.2% to 60.2% (p < 0.05). The AVP was effective across various demographic and economic subgroups, demonstrating its generalizability. ITSA findings indicated the AVP improved HPV vaccination initiation and completion rates in clinic settings and that AVP strategies facilitated resilience during the pandemic. The minimal adaptation required for implementation in a new clinic system underscores its feasibility and potential for widespread adoption. Full article

Globally, there has been little growth in vaccination coverage, with countries in the Horn of Africa having the lowest vaccination rates. This study investigated factors associated with vaccination status among children under five years old in Somaliland. The 2020 Somaliland Demographic and Health Survey surveyed women aged 15–49 years from randomly selected households. This multilevel analysis included 2673 primary caregivers of children under five. Only 34% of children were ever vaccinated. Childhood vaccination coverage was positively associated with high-budget regions, high healthcare facility density, and children older than 23 months. Vaccination coverage was greater for urban and rural residents than for nomadic people. Children whose mothers could read part of one sentence or one complete sentence were more likely to be vaccinated than illiterate mothers. Children whose mothers received antenatal care (ANC) once, two to three times, or four times or more were more likely to be vaccinated than those whose mothers received no ANC. Childhood vaccination coverage in Somaliland is low. Promoting maternal ANC visits and increasing women’s literacy may enhance vaccination coverage. Funds should be allocated to areas with low resources, particularly for nomadic people, to boost vaccination uptake. Full article