Human Vaccine Research Articles

Towards 90-70-90 targets: Individual and community level factors associated with cervical cancer screening among women of reproductive age in Tanzania: A multi-level analysis based on 2022 Tanzania demographic and health survey.

Cervical cancer is a major public health problem worldwide, and is mainly caused by human papillomaviruses. More than 90% of cervical cancer cases can be prevented by using a human papilloma vaccine and screening. Despite the ongoing global cervical cancer screening target, uptake remains unacceptably low in sub-Saharan Africa such as Tanzania. Although cervical cancer is the leading cause of mortality in Tanzania, evidence on the individual- and community-level factors associated with cervical cancer screening among women of reproductive age is scarce. Therefore, this study aimed to determine the individual- and community-level factors associated with cervical cancer screening among women of reproductive age in Tanzania. This study used data from the 2022 Tanzania Demographic and Health Survey (TDHS). A weighted sample of 15,140 women of reproductive age was included in this study. Given the effect of clustering and binary nature of the outcome variable, we used a multilevel binary logistic regression model. The adjusted odds ratio (AOR) with 95% Confidence Interval (CI) was statistically significant. Moreover, the model with the lowest deviance best suited the data. The overall uptake of cervical cancer screening among Tanzanian women was 7.28% (95% confidence interval [CI]: 6.87%, 7.70%). Women's age (25-34, 35-49), women with primary, secondary, and higher educational levels, being employed, a high household wealth index, visiting health facilities in the last 12 months, owning mobile phones, urban residence, and southern highlands, Southern, and Zanzibar administrative zones, were significantly associated with cervical cancer screening. Cervical cancer screening among women in Tanzania was low. Low uptake underscores the need for increased focus on addressing the coverage of the 2030 Sustainable Development Goals (SDGs). The study would help policymakers create programs that consider education, employment, visiting health facilities, mobile phones, wealth, residence, and administrative zones, which would make women undergo cervical cancer screening. Pointing to women living with low cervical cancer screening could help increase their uptake and achieve the targets of the national and World Health Organization.

Practical Management of ANCA-associated Vasculitis – A Clinician’s Perspective

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can be a life-threatening condition, characterised by necrotising inflammation of small blood vessels. Major organ involvement, most commonly kidney and lung disease, is associated with significant morbidity and mortality. Intensive early immunosuppressive therapy is the cornerstone of management and has transformed ANCA-associated vasculitis (AAV) into a chronic relapsing condition. Remission induction with tapering glucocorticoids in combination with cyclophosphamide or rituximab is the standard of care for severe disease. Avacopan, an oral C5aR1 antagonist, has been approved for remission induction and helps minimise glucocorticoid exposure. Plasma exchange should be considered for severe kidney or life-threatening disease. Lower dose glucocorticoid induction regimens can be used without compromising remission rates. Remission maintenance therapy is recommended, and rituximab is usually first line over azathioprine. Mycophenolate mofetil (MMF) or methotrexate with low dose glucocorticoids are third line options. Immunosuppression associated infection risk remains a concern; both during acute presentations and in the long term; highlighted by the impact of rituximab on humoral immunity and vaccine response during the COVID-19 pandemic. There remains an ongoing need for therapies which induce rapid remission and optimise kidney recovery whilst minimising infection risk. Clinical trials are evaluating newer therapeutic options. Due to increasing treatment options, management should be individualised, balancing effective immunosuppression against co-morbidities and frailty. Summary: This review focuses on the treatment decision pathways for clinicians and patients in the management of severe AAV (granulomatosis with polyangiitis and microscopic polyangiitis). Key clinical trials, predictors of outcome, novel therapeutics and practical steps to mitigate infection risk are discussed. Key messages: Immunosuppression regimens have been refined due to emerging evidence from clinical trials. Rituximab, avacopan and reduced-dose glucocorticoid schedules have been the focus of recent studies. Infections and immunosuppression-induced immunodeficiency must be considered when determining individualised treatment.

Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses

Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4+ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4+ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4+ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4+ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.

Vaccination Coverage for Medically Indicated Vaccines in a Convenience Sample of Severely Immunocompromised Patients with COVID-19: An Observational Cohort Study

Background: In recent decades, the number of immunocompromised patients (ICPs) has increased significantly. ICPs have an impaired immune system, making them susceptible to complicated infections. To protect them from infections, ICPs are eligible to receive several medically indicated vaccines. To obtain insight into the uptake of these medically indicated vaccines, we determined the coverage of these vaccines in ICPs. Methods: This observational cohort study was conducted at the University Medical Centre Utrecht, the Netherlands, from September 2021 to April 2022. All adult ICPs admitted for COVID-19 were asked to complete a questionnaire on their vaccination history (pneumococcal, herpes zoster, human papillomavirus vaccination, influenza, and COVID-19 vaccines) and history of vaccine-preventable infections. In addition, patients’ vaccination history was reviewed in medical files. Results: A total of 115 patients completed the questionnaire and were included. Although all patients had an indication for pneumococcal vaccination, only 22 received it (19%). Coverage for herpes zoster was low (1%, 1/106 eligible patients). Coverage for human papillomavirus vaccination (HPV) was also low (40%, two out of five eligible patients). In contrast, 92% of patients received vaccination against SARS-CoV-2, and 77% of patients received seasonal influenza vaccination. Conclusions: Although coverage for influenza and COVID-19 vaccination was high in ICPs, coverage for other medically indicated vaccines was low. Identifying which factors contributed to high COVID-19 and influenza vaccine uptake can help to improve vaccination rates for the other recommended vaccines. Clear guidelines for clinicians and the removal of organizational obstacles are needed to improve vaccination coverage.

Evaluation of the Efficacy of the Vaccine Production Process in Removing Residual Host Cell DNA from the Vero Cell Rabies Vaccine

Background: The Vero cell rabies vaccine is currently the most widely used human rabies vaccine. However, owing to the presence of residual host cell DNA (HCD) in the final product and the potential tumorigenicity of the DNA of high-passage Vero cells, the WHO not only sets a limit on the number of times cells used in production can be passaged, but also imposes strict requirements on the amount of residual HCD in the final vaccine product. Objectives: To systematically reduce the HCD level in the final vaccine product, multiple purification steps are included in the vaccine production process. This study investigated the effectiveness of key production steps in antigen recovery and DNA removal. Methods: The residual HCD fragment content and size distribution were detected using fluorescence quantitative PCR (qPCR) and capillary gel electrophoresis (CGE), and the rabies virus glycoprotein antigen content was detected using enzyme-linked immunosorbent assay (ELISA). The antigen recovery rate and HCD removal rate in each key process were calculated to evaluate the scientific basis and effectiveness of each production step. Additionally, the stability of the process was studied using multiple commercial batches of the product. Results: The results revealed that the total antigen recovery rate in the production process described in this report was no less than 8.5%, and the effective removal rate of residual HCD was not lower than 99.99%. Moreover, the amount of residual HCD in the final product was far below the quality standard of 2 ng/dose, and most of the residual HCD fragments were smaller than 200 bp. The results of the process stability studies on multiple commercial batches showed that the bulk human rabies vaccine produced by this process had excellent safety and efficacy and that the production process was stable and thus suitable for large-scale batch production. Conclusions: The production process described in this study achieved effective recovery of viral antigens and efficient removal of residual HCD, and the process was stable and controllable, enabling the continuous and stable production of vaccine products that meet WHO recommendations and the relevant requirements of the current edition of the Chinese Pharmacopeia. In addition, this study provides theoretical guidance for optimizing the vaccine production process.

Non-inferiority study of purified Vero rabies vaccine - serum free in three-dose and two-dose pre-exposure prophylaxis regimens in comparison with licensed rabies vaccines.

A next-generation, serum-free, highly purified Vero cell rabies vaccine, PVRV-NG2, is in development. This multicenter, observer-blind, phase 3 study evaluated the immunogenicity and safety of PVRV-NG2, compared with two licensed rabies vaccines (purified Vero cell rabies vaccine [PVRV] and human diploid cell vaccine [HDCV]), as a pre-exposure prophylaxis (PrEP) regimen. Participants were randomized 3:1:1 to PVRV-NG2, PVRV, or HDCV, as a three-dose (Cohort 1; children and adults; day [D] 0, D7, and D28) or two-dose (Cohort 2; adults; D0 and D7) PrEP regimen. The primary objective was non-inferiority of PVRV-NG2 to PVRV and HDCV as three-dose PrEP, based on the proportion of participants with rabies virus neutralizing antibody (RVNA) titer ≥0.5 IU/mL at D42. Non-inferiority of immune response for two-dose PrEP at D28, and non-inferiority of two-dose (D28) versus three-dose (D42) HDCV were also assessed as secondary immunogenicity objectives. Safety was assessed throughout. Overall, 1708 participants were enrolled (Cohort 1: 505 children, 505 adults; Cohort 2: 698 adults). All participants had RVNA titers ≥0.5 IU/mL after three-dose PVRV-NG2 (D42), with non-inferiority to PVRV and HDCV demonstrated. All secondary immunogenicity objectives were achieved, including non-inferiority of two-dose PVRV-NG2 versus two-dose PVRV and HDCV (D28) and three-dose HDCV (D42), and non-inferiority of two-dose HDCV versus three-dose HDCV. The safety profile of PVRV-NG2 was comparable to those of PVRV and HDCV. This study supports the use of PVRV-NG2 in two- or three-dose PrEP regimens, with no safety concerns identified. ClinicalTrials.gov identifier: NCT04127786; EudraCT: 2019-000973-22; WHO: U1111-1217-3241.

Predicting leishmaniasis outbreaks in Brazil using machine learning models based on disease surveillance and meteorological data

Leishmaniasis poses a significant global health concern due to the absence of vaccines for humans and high infection rates in some countries. It is classified as a neglected tropical disease. In 2022, roughly 85% of global visceral leishmaniasis cases were reported in seven countries: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan, and Sudan. Despite Brazil’s advanced medical capabilities compared to other affected regions, certain areas still witness a significant number of cases, prompting increased attention from researchers and raising concerns within the healthcare system. This study explores the application of artificial intelligence algorithms, particularly machine learning (ML) models to predict leishmaniasis outbreaks in selected Brazilian cities based on accumulated cases from 2007 to 2022, leveraging available meteorological data to enhance model accuracy. Our investigation concentrated on the following cities in Brazil: Fortaleza/CE, Teresina/PI, and São Luís/MA were chosen for the study of visceral leishmaniasis, whereas Manaus/AM, Rio Branco/AC, and Macapá/AP were selected for the study of tegumentary leishmaniasis, encompassing both cutaneous and mucocutaneous forms. Several Artificial Neural Network (ANN) architectures were evaluated, including a Simple Feedforward Neural Network (SFNN), a Deep Feedforward Neural Network (DFNN), and a Long Short-Term Memory (LSTM) recurrent neural network. Additionally, the Support Vector Machine (SVM), specifically the Support Vector Regression (SVR), was tested. Various metrics were used to identify the most effective models, in which the Root Mean Squared Error (RMSE) was the primary one. The results highlight the significance of meteorological data as a crucial factor in ML models for predicting leishmaniasis outbreaks, while also emphasizing the importance of fine-tuning these models to achieve greater accuracy. Finally, data and the pseudo-code of the models are accessible through an open repository to encourage further studies in this area.

Obesity does not influence SARS-CoV-2 humoral vaccine immunogenicity

Obesity is a recognized factor influencing immune function and infectious disease outcomes. Characterization of the influence of obesity on SARS-CoV-2 humoral vaccine immunogenicity is required to properly tailor vaccine type (mRNA, viral-vector, protein subunit vaccines) and dosing schedule. Data from a prospective cohort study collected over 34 months was used to evaluate the slope of antibody production and decay and neutralizing capacity following SARS-CoV-2 vaccination in individuals with and without obesity at baseline. Most participants were female (65.4%), white (92.4%), and received mRNA vaccines. 210 were obese and 697 non-obese. Sex and infection-acquired immunity were identified as effect modifiers for the relationship between obesity and COVID-19 vaccine humoral immunogenicity. No consistent influence of obesity on peak titres, titre retention, antibody isotype (IgG, IgM, IgA), or neutralization was identified when controlling for other key variables. It may not be necessary to consider this variable when developing SARS-CoV-2 vaccine dosing strategies.

A Lassa virus live attenuated vaccine candidate that is safe and efficacious in guinea pigs

Lassa virus (LASV) is a rodent-borne mammarenavirus that causes tens to hundreds of thousands of human infections annually in Western Africa. Approximately 20% of these infections progress to Lassa fever (LF), an acute disease with case–fatality rates from ≈20–70%. Currently, there are no approved vaccines or specific therapeutics to prevent or treat LF. The LASV genome consists of a small (S) segment that has two genes, GP and NP, and a large (L) segment that has two genes, L and Z. In both segments, the two genes are separated by non-coding intergenic regions (IGRs). Recombinant LASVs (rLASVs), in which the L segment IGR was replaced with the S segment IGR or in which the GP gene was codon-deoptimized, lost fitness in vitro, were highly attenuated in vivo, and, when used as vaccines, protected domesticated guinea pigs from otherwise lethal LASV exposure. Here, we report the generation of rLASV/IGR-CD, which includes both determinants of attenuation and further enhances the safety of the vaccine compared with its predecessors. rLASV/IGR-CD grew to high titers in Vero cells, which are approved for human vaccine production, but did not cause signs of disease or pathology in guinea pigs. Importantly, guinea pigs vaccinated with rLASV/IGR-CD were completely protected from disease and death after a typically lethal exposure to wild-type LASV. Our data support the development of rLASV/IGR-CD as a live-attenuated LF vaccine with stringent safety features.

Bioinformatics analysis to design a multi-epitope mRNA vaccine against S. agalactiae exploiting pathogenic proteins

Antibiotic resistance in bacterial pathogen infections is a growing global issue that occurs due to their adaptation to changing environmental conditions. Therefore, producing an efficient vaccine as an alternative approach can improve the immune system, eradicate related pathogens, and overcome this growing problem. Streptococcus agalactiae belongs to group B Streptococcus (GBS). Colonization of GBS during pregnancy is a significant risk factor for infants and young children. S. agalactiae infected population exhibits resistance to beta-lactams, including penicillin and the second-line antibiotics erythromycin and clindamycin. On the other hand, there are currently no commercial vaccines against this pathogen. Vaccination of pregnant women is a highly effective method to protect newborns and infants from S. agalactiae infection, and it has been identified as an urgent demand by the World Health Organization. This study employed various immunoinformatic tools to develop an effective vaccine that could trigger both humoral and cell-mediated immunity and prevent disease. For this purpose, three conserved antigenic proteins of the main pathogenic strains of S. agalactiae were utilized to predict CTL, HTL, and B-cell epitopes for producing an mRNA vaccine against different strains of S. agalactiae. The selected epitopes were fused using proper linkers. The Resuscitation promoting factor E (RpfE) sequence was incorporated in the designed vaccine construct as an adjuvant to boost its immune response. Different physicochemical characteristics of the final designed vaccine, modeling of the three-dimensional structure, molecular docking, molecular dynamics simulation, and immunological response simulation were screened following vaccine administration in an in vivo model. Computational immune simulation data identified that IgG1, IgM, INF γ, IL-2, T helper, and B-cell populations increased significantly after vaccination. These findings suggested that the vaccine candidate may provide good protection against S. agalactiae infection. However, experimental and animal model studies are required for additional validation and implementation in human vaccination programs.

Safety and immunogenicity of freeze-dried human rabies vaccines: A phase 3 clinical trial of Zagreb and Essen regimes

ABSTRACT Recently optimized freeze-dried rabies vaccines (Vero cell) are promising for rabies prevention; however, comparisons of Essen 5-dose and Zagreb 4-dose regimens are needed for clinical applications. This phase III clinical trial aimed to assess the safety and immunogenicity of candidate freeze-dried rabies vaccines developed for human use by Shandong Yeedo Biotechnology (Registration No.: CTR20182016, http://www.chinadrugtrials.org.cn/index.html). In total, 40 participants in stage I and 1797 subjects in stage II with an age range of 10–60 years were recruited. Both 4-dose and 5-dose experimental vaccines were well-tolerated in stage 1, with similar overall adverse event (AE) rates. In stage 2, systemic fever (35.39%) and local pain (48.91%) were common, and the rate of Grade 3 AEs was approximately 2.5%. Rates of local reactions and unsolicited AEs differed among groups (p = .045 and 0.011). Immunogenicity analyses showed higher antibody levels, seroconversion rates, and pre-immune seroconversion rates in the 4-dose experimental group versus the 5-dose group (p < .001) on day 7 post-first dose, with similar GMCs (geometric mean concentrations) by day 14. Pre-immune negative subjects had comparable antibody levels in the 4-dose and 5-dose experimental groups, outperforming the 5-dose control group (p = .039). The rate difference (95% CI) for first-dose seroconversion at 14 days post-vaccination among pre-immune antibody-negative subjects indicated non-inferiority between the 5-dose experimental and control groups. Overall, the Shandong Yeedo rabies vaccine demonstrated satisfactory safety and efficacy, offering a new option for rabies prevention.

Freund’s adjuvant is a classic of vaccine adjuvants and the basis of experimental immunology

Background. The invention of vaccines is rightfully considered one of the triumphs of medical research and one of the most remarkable achievements in public health in the history of humanity. According to the World Health Organization, vaccination saves 5 lives every minute and has saved over 25 million lives from 2011 to 2020. The effectiveness of a vaccine depends not only on the components of the antigen but also on the adjuvants, which are often used for more effective stimulation of the immune system. Purpose – to characterize the modern understanding of vaccine adjuvants, particularly Freund’s adjuvant, as a foundation of experimental immunology based on open source information. Materials and Methods. The selection of publications was conducted using databases such as PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and others, which provided information on vaccine adjuvants, particularly Freund’s adjuvant. In the first stage, a search for literature sources was performed using keywords: vaccine adjuvants, complete Freund’s adjuvant, alum, adjuvant arthritis, experimental immunology. In the second stage, the abstracts of the articles were reviewed, and publications that did not meet the research criteria were excluded. In the third stage, the full texts of the selected articles were examined for compliance with the inclusion criteria and relevance of the studies. Results. In 1924, G. Ramon demonstrated that the co-administration of the diphtheria anatoxin he had recently developed with other compounds such as tapioca, lecithin, agar, starch oil, saponin, and others enhances antitoxin reactions to diphtheria. In 1942, J. Freund developed a potent adjuvant in the form of a water-in-oil emulsion using mineral oil that contained heat-killed mycobacteria (Mycobacterium tuberculosis), which was named complete Freund’s adjuvant. However, over time, Freund’s adjuvant was banned for use in vaccines for humans due to its toxicity. Despite numerous studies, until 2009, aluminum salts dominated the use of adjuvants in licensed vaccines. Beginning in 2010, the demand for the development of new adjuvants noticeably increased, especially following several pandemics such as Ebola, Zika, and COVID-19. It is known that adjuvants enhance the adaptive immunity of vaccines by activating innate immune cells. The main concept of their effect is that adjuvants promote the production of antigen presentation signals and costimulatory signals by activating antigen-presenting cells. The model of adjuvant arthritis induced by complete Freund’s adjuvant was created to study the pathogenesis of arthritis, including rheumatoid arthritis, gout, and osteoarthritis, as well as to evaluate the effectiveness of certain anti-arthritis and anti-inflammatory drugs. Conclusions. Vaccine adjuvants encompass a wide range of chemical compounds and substances that enhance immune responses through physical or chemical binding with antigens. The most significant influences on the formation of the modern understanding of vaccine antigens and immunology in the 20th century were Gaston Ramon (1886–1963), Alexander Glenny (1882–1965), and Jules Freund (1890–1960). Complete Freund’s adjuvant has historically been and remains one of the most useful tools for immunologists. The use of antigenic mixtures from biological tissue extracts along with complete Freund’s adjuvant allows for the reproduction of various organ-specific autoimmune diseases in laboratory animals (such as autoimmune arthritis, myocarditis, hepatitis, thyroiditis, encephalomyelitis, etc.), facilitating preclinical studies on the effectiveness of potential immunomodulating and symptomatic therapeutic agents.

Understanding American tegumentary leishmaniasis in urban Montes Claros, Brazil: insights from clinical, immunological and therapeutic investigations.

The challenge of American tegumentary leishmaniasis (ATL) continues in Brazil, presenting a persistent public health issue despite initiatives aimed at public outreach, vector control and health education. To gain a deeper understanding of this disease, a study was conducted in an endemic region located in the northern region of the state of Minas Gerais, Brazil. The study monitored 30 resident patients diagnosed with ATL, using serum samples from 6 healthy individuals as controls. The localized cutaneous form of the disease was found to be predominant, with lesions appearing on various parts of the body and the majority of the affected individuals being male. The study found significantly higher levels of IgG anti-α-Gal antibodies in ATL-infected patients compared to healthy individuals. Treatment of 19 patients with meglumine antimoniate resulted in limited improvement in symptoms for most. Nonetheless, the study found that 12 patients who completed treatment with epithelialization of the lesions showed a significant decrease in IgG anti-α-Gal antibodies, indicating potential applications of this antibody in the diagnosis and monitoring of the disease. The study also identified Leishmania species in 7 analysed patients, revealing 6 cases infected by Leishmania braziliensis and 1 by L. infantum, with a significant difference in the anti-α-Gal responses. The findings of the study emphasize the urgent need for the development of human vaccines and innovative treatment strategies adapted to the diversity of Leishmania species causing cutaneous leishmaniasis and individual patient responses to improve the clinical management of ATL in Brazil and similar endemic regions.

The Apparent Lack of the Risk of Intussusception Immediately After Rotavirus Vaccination Among Japanese Infants.

Rotavirus vaccines carry a small risk of intussusception mainly 1-7 days after vaccination in the United States of America, Europe, Australia, and Latin America where the background rate of intussusception is relatively low. Such risks are undetectable in Africa and India where the background rate is the lowest. Because few studies were carried out in high-background-rate countries such as Japan, we examined how intussusception occurred in infants living in Akita prefecture, Japan, while the vaccines were sold in the private market. Between 2011 and 2018, an estimated 21,677 infants (46%) were vaccinated and 54% were not. Through a retrospective survey of medical records in 18 hospitals in the prefecture, we identified 58 infants, 28 of whom were vaccinated and 30 of whom were unvaccinated, as having intussusception that met level 1 of the Brighton criteria. Thus, the intussusception rate was 123 per 100,000 infant-years (95% confidence interval [CI]: 94-160). Despite the high rate, none developed intussusception 1-7 days after the first dose of either the monovalent human rotavirus vaccine (GSK) or the pentavalent human-bovine reassortant vaccine (MSD). The incidence rate ratio of vaccinated to unvaccinated infants between 42 and 245 days of life was estimated at 0.96 (95%CI: 0.43-2.1; p = 0.92). Given that over 95% of infants received the first dose before 15 weeks of age, the risk of intussusception associated with the rotavirus vaccines in high-incidence-rate countries can be reduced to a minimum by adhering to the recommended schedule at 2, 3, and 4 months of age.

Oceanic Breakthroughs: Marine-Derived Innovations in Vaccination, Therapy, and Immune Health.

The vast, untapped potential of the world's oceans is revealing groundbreaking advancements in human health and vaccination. Microalgae such as Nannochloropsis spp. and Dunaliella salina are emerging as resources for recombinant vaccine development with specific and heterologous genetic tools used to boost production of functional recombinant antigens in Dunaliella salina and Nannochloropsis spp. to induce immunoprotection. In humans, several antigens produced in microalgae have shown potential in combating diseases caused by the human papillomavirus, human immunodeficiency virus, hepatitis B virus, influenza virus, Zika virus, Zaire Ebola virus, Plasmodium falciparum, and Staphylococcus aureus. For animals, microalgae-derived vaccine prototypes have been developed to fight against the foot-and-mouth disease virus, classical swine fever virus, vibriosis, white spot syndrome virus, and Histophilus somni. Marine organisms offer unique advantages, including the ability to express complex antigens and sustainable production. Additionally, the oceans provide an array of bioactive compounds that serve as therapeutics, potent adjuvants, delivery systems, and immunomodulatory agents. These innovations from the sea not only enhance vaccine efficacy but also contribute to broader immunological and general health. This review explores the transformative role of marine-derived substances in modern medicine, emphasizing their importance in the ongoing battle against infectious diseases.

Design, Development and Immunogenicity Study of a Multi-Epitope Vaccine Prototype Against SARS-CoV-2.

Objectives: SARS-CoV-2 caused the COVID-19 pandemic, which overwhelmed global healthcare systems. Over 776 million COVID-19 cases and more than 7 million deaths were reported by WHO in September 2024. COVID-19 vaccination is crucial for preventing infection and controlling the pandemic. Here, we describe the design and development of a next-generation multi-epitope vaccine for SARS-CoV-2, consisting of T cell epitopes. Methods: Immunoinformatic methods were used to derive models for the selection of MHC binders specific for the mouse strain used in this study among a set of human SARS-CoV-2 T cell epitopes identified in convalescent patients with COVID-19. The immunogenicity of the vaccine prototype was tested on humanized-ACE2 transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J mice by in vitro, in vivo, and ex vivo immunoassays. Results: Eleven binders (two from the Envelope (E) protein; two from the Membrane (M) protein; three from the Spike (S) protein; and four from the Nucleocapsid (N) protein) were synthesized and included in a multi-epitope vaccine prototype. The animals were immunized with a mix of predicted MHC-I, MHC-II, or MHC-I/MHC-II peptide epitopes in Complete Freund's Adjuvant, and boosted with peptides in Incomplete Freund's Adjuvant. Immunization with SARS-CoV-2 epitopes remodeled the lymphocyte profile. A weak humoral response and the significant production of IL-4 and IFN-γ from T cells were found after the vaccination of the animals. Conclusions: The multi-epitope vaccine prototype presented in this study demonstrates immunogenicity in mice and shows potential for human vaccine construction.

Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection.

Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein-directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti-spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2-infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection.

Recombinant receptor-binding motif of spike COVID-19 vaccine candidate induces SARS-CoV-2 neutralizing antibody response

Introduction: The SARS-CoV-2 pandemic necessitates effective therapeutic solutions. The receptor-binding motif (RBM) is a subdomain of the spike protein's receptor-binding domain (RBD) and is critical for facilitating the binding of SARS-CoV-2 to the human ACE2 receptor. This study investigates the use of the receptor-binding motif (RBM) domain as an immunogen to produce potent neutralizing antibodies against SARS-CoV-2. Methods: The RBM gene was codon-optimized and cloned into the pET17b vector for expression in E. coli BL21 (DE3) cells, induced with 1 mM IPTG. The recombinant RBM protein was purified using Ni-NTA affinity chromatography. After validating the recombinant RBM by Western blotting with anti-His tag antibodies, BALB/c mice were immunized with 20 µg of the purified RBM protein. Anti-RBM IgG was subsequently purified using protein G resin, and its neutralizing capacity was assessed using the Pishtaz Teb Zaman Neutralization Assay Kit. Results: The recombinant RBM protein, with a molecular weight of 10 kDa, was expressed as inclusion bodies. the typical yield of purification was 27 mg/L of bacterial culture. The neutralization test demonstrated a concentration of 36 µg/mL of neutralizing antibodies in the immunized serum, preventing the spike protein from binding to ACE2. Conclusion: Our study demonstrated that anti-RBM antibodies exhibited neutralization effects on SARS-CoV-2. These findings provide evidence for the development of a vaccine candidate through the induction of antibodies against the RBM, necessitating further studies with adjuvants suitable for human use to evaluate its potential for human vaccination.

New insights for the development of efficient DNA vaccines.

Despite the great potential of DNA vaccines for a broad range of applications, ranging from prevention of infections, over treatment of autoimmune and allergic diseases to cancer immunotherapies, the implementation of such therapies for clinical treatment is far behind the expectations up to now. The main reason is the poor immunogenicity of DNA vaccines in humans. Consequently, the improvement of the performance of DNA vaccines invivo is required. This mini-review provides an overview of the current state of DNA vaccines and the various strategies to enhance the immunogenic potential of DNA vaccines, including (i) the optimization of the DNA construct itself regarding size, nuclear transfer and transcriptional regulation; (ii) the use of appropriate adjuvants; and (iii) improved delivery, for example, by careful choice of the administration route, physical methods such as electroporation and nanomaterials that may allow cell type-specific targeting. Moreover, combining nanoformulated DNA vaccines with other immunotherapies and prime-boost strategies may help to enhance success of treatment.

Human papillomavirus prophylactic vaccines: update on new vaccine development and implications for single-dose policy.

Human papillomavirus (HPV) prophylactic vaccines were first licensed in 2006 with the primary goal of preventing HPV-related cancers, with cervical cancer accounting for the highest morbidity and mortality globally. Six HPV vaccines have been licensed; 4 of these have been prequalified by the World Health Organization, and additional products are in the pipeline. This article provides an overview of HPV vaccine coverage and current and anticipated vaccine supply vs expected demand. Given that the 2022 World Health Organization position paper on HPV vaccines includes a 1-dose regimen as an alternate schedule, we will discuss the evidence for using licensed vaccines in single-dose regimens and the approach to generating similar supportive data for other current and future vaccines. The broad adoption of a single-dose HPV vaccine regimen would expand access to vaccines by improving the supply-demand balance, increasing affordability, and simplifying logistics, which will ultimately impact HPV-related morbidity and mortality.