Innovative Vaccine Research Articles

Hepatitis B Therapeutic Vaccine: A Patent Review.

Viral hepatitis has long been underrated as a danger to global health. The UN only recently called for worldwide action to tackle viral hepatitis and lessen the disease burden in its "2030 Agenda for Sustainable Development". Hepatitis B virus (HBV), which causes liver cirrhosis and malignancy, is a main cause of death globally. This review analyses innovative HBV therapeutic vaccine candidates for which a patent was filed between January 2010 and March 2022 and presents future improvement techniques for vaccine efficacy. Although there is a preventative vaccine for HBV infection, over 3% of people worldwide have the disease on a long-term basis and can no longer benefit from it. Most people will have chronic HBV infection for the rest of their lives once it has been diagnosed. Moreover, only a small percentage of treated patients experience a functional cure with persistent hepatitis B surface antigen reduction. A significant proportion of deaths are caused by liver cirrhosis and hepatocellular cancer, which are both caused by chronic hepatitis B infection. Hence, there is an urgent need for novel medications due to the inadequacies of the current therapies.

Reducing Hospital Capacity Needs for Seasonal Respiratory Infections: The Case of Switching to High-Dose Influenza Vaccine for Dutch Older Adults

ObjectivesInfluenza is responsible for considerable health and economic burden every year. Especially older adults are vulnerable for influenza infection and its complications due to immunosenescence and often-underlying medical conditions. Recently, the innovative quadrivalent high-dose influenza vaccine (QIV-HD) has become available in Europe. Through its enhanced immunogenicity, QIV-HD offers improved protection for older adults against respiratory as well as cardiovascular complications. We estimated the potential impact—specifically in terms of hospital admissions and related costs—of a hypothetical past switch from QIV-Standard dose (SD) to QIV-HD in The Netherlands. MethodsEstimates of hospitalizations for the older adults vaccinated with QIV-SD were derived from the seasons 2010/2011-2017/2018. Subsequently, the number of respiratory infections and cardiovascular complications of influenza were estimated for the year 2019/2020 for both QIV-SD and QIV-HD. To calculate the overall corresponding savings, costs for hospital complications, derived from literature, were used. ResultsWhen QIV-HD would have been used instead of QIV-SD during the season 2019/2020, an additional 220 hospitalizations would have been averted among older adults of 60 years and older in the Netherlands. This corresponds to savings of €1 219 779 (uncertainty interval: 1 089 813-1 348 549), of which 69% is attributable to cardiovascular-related hospitalizations. ConclusionsWe demonstrate that a relevant improvement in influenza vaccination among older adults in The Netherlands can be achieved by switching from the current QIV-SD to QIV-HD. Not only comes a switch from QIV-SD to QIV-HD with a significant reduction in pressure on hospital capacity but also with notable cost savings.

Urgency and necessity of Epstein-Barr virus prophylactic vaccines.

Epstein-Barr virus (EBV), a γ-herpesvirus, is the first identified oncogenic virus, which establishes permanent infection in humans. EBV causes infectious mononucleosis and is also tightly linked to many malignant diseases. Various vaccine formulations underwent testing in different animals or in humans. However, none of them was able to prevent EBV infection and no vaccine has been approved to date. Current efforts focus on antigen selection, combination, and design to improve the efficacy of vaccines. EBV glycoproteins such as gH/gL, gp42, and gB show excellent immunogenicity in preclinical studies compared to the previously favored gp350 antigen. Combinations of multiple EBV proteins in various vaccine designs become more attractive approaches considering the complex life cycle and complicated infection mechanisms of EBV. Besides, rationally designed vaccines such as virus-like particles (VLPs) and protein scaffold-based vaccines elicited more potent immune responses than soluble antigens. In addition, humanized mice, rabbits, as well as nonhuman primates that can be infected by EBV significantly aid vaccine development. Innovative vaccine design approaches, including polymer-based nanoparticles, the development of effective adjuvants, and antibody-guided vaccine design, will further enhance the immunogenicity of vaccine candidates. In this review, we will summarize (i) the disease burden caused by EBV and the necessity of developing an EBV vaccine; (ii) previous EBV vaccine studies and available animal models; (iii) future trends of EBV vaccines, including activation of cellular immune responses, novel immunogen design, heterologous prime-boost approach, induction of mucosal immunity, application of nanoparticle delivery system, and modern adjuvant development.

Induction of a strong and long-lasting neutralizing immune response by dPreS1-TLR2 agonist nanovaccine against hepatitis B virus

Hepatitis B virus remains a major medical burden with more than 250 million chronically infected patients worldwide and 900,000 deaths each year, due to the disease progression towards severe complications (cirrhosis, hepatocellular carcinoma). Despite the availability of a prophylactic vaccine, this infection is still pandemic in Western Pacific and African regions, where around 6% of the adult population is infected. Among novel anti-HBV strategies, innovative drug delivery systems, such as nanoparticle platforms to deliver vaccine antigens or therapeutic molecules have been investigated. Here, we developed polylactic acid-based biodegradable nanoparticles as an innovative and efficient vaccine. They are twice functionalized by (i) the entrapment of Pam3CSK4, an immunomodulator and ligand to Toll-Like-Receptor 1/2, and by (ii) the adsorption/coating of myristoylated (2–48) derived PreS1 from the HBV surface antigen, identified as the major viral attachment site on hepatocytes. We demonstrate that such formulations mimic HBV virion with an efficient peptide recognition by the immune system, and elicit potent and durable antibody responses in naive mice during at least one year. We also show that the most efficient in vitro viral neutralization was observed with NP-Pam3CSK4-dPreS1 sera. The immunogenicity of the derived HBV antigen is modulated by the likely synergistic action of both the dPreS1 coated nanovector and the adjuvant moiety. This formulation represents a promising vaccine alternative to fight HBV infection.

Vaccine Innovation for Dengue, Chikungunya, Zika and Yellow Fever: Accelerating Global Development Agenda and Partnerships in Post-COVID Era

Vaccine Innovation for Dengue, Chikungunya, Zika and Yellow Fever: Accelerating Global Development Agenda and Partnerships in Post-COVID Era

HIV Vaccine Trials in Thailand and Path to HIV Cure

Thailand has had over 30 years of experiences and development in fighting HIV/AIDS with successful results in terms of providing access to revention, testing, antiretroviral treatment (ART) and care for over 90% of the affected patients. As a consequence, approximately 400,000 patients on ART currently have undetectable viral load, lead normal lives, and are untransmittable. However, ART must remain in place forever or else the viral load in blood will rebound. Recent advance in stem cell transplant, gene editing, and therapeutic HIV vaccine development yields hope on designing novel approach for an HIV elimination or functional cure. The National AIDS Prevention and Alleviation Committee of Thailand has set up the Subcommittee on HIV Vaccine Trials to oversee and endorse experimental vaccine regimen with sound and adequate scientific background to be tested in Thailand. So far, at least 23 small and large studies have been conducted in collaboration with the international organizations and at least 10 articles were published after the studies ended and cited over 2,726 times. One landmarked trial using notable vaccine regimen, evaluated in the RV144 trial, has shown effectiveness in reducing new infections by 31.2%. The conduction of these research in Thailand have facilitated the development of infrastructure, networking, and experience sufficiently to further support future field trial with a notable HIV cure approach. Since there are over 400,000 HIV cases with undetectable viral load in Thailand, this condition poses an excellent opportunity for testing a novel HIV cure approaches to eliminate HIV or functional HIV cure. The Subcommittee has reviewed current novel methods in this regard and strongly welcomed international organizations with similar aim, to test an innovative therapeutic HIV vaccine or a combination therapy to finally end HIV/AIDS in Thailand by the year 2030. Keywords: HIV vaccine; HIV cure; Latent HIV reservoir; mRNA vaccine; Gene therapy; Stem cell transplantation

Access to vaccines: how can we leverage technology innovations to achieve greater vaccine equity?

Fatema Kazi is an Immunologist working at the WHO’s R&D Blueprint Team–part of the Health Emergencies and Preparedness Response. Previously, she has worked at the Elizabeth Glaser Pediatric AIDS Foundation, GAVI, UNOPS, The Stop TB Partnership, and the Global TB Programme (WHO) focusing on research and development in innovative therapeutics, vaccines, and diagnostics. She has a PhD in Cellular Immunology and Infectious Diseases from the London School of Hygiene and Tropical Medicine, and pursued her postdoctoral career as a Senior Immunologist Research Fellow at Leiden University Medical Centre and the University of Oxford, as well as training as a molecular biologist for the Ministry of Defense, UK. In response to the pandemic, Fatema has been leading projects at WHO related to tracking, monitoring, and assessing the development of the COVID-19 vaccine candidates worldwide, conducting epidemiological reviews of vaccine effectiveness against variants of concern. She is now evaluating vaccines for Monkeypox, Lassa Fever and Sudan ebolavirus in response to the current outbreaks.Fatema Kazi works for the WHO, where she helps to assess the public health value of vaccine products and technologies in routine, campaign, and outbreak settings. We caught up with her to discuss how innovations in vaccine technology can help get vaccines to the people who need them.

The value of public-private collaborative real-world evidence platforms to monitor vaccine performance post authorization: DRIVE - a European initiative

ABSTRACT Introduction Fighting pandemics requires an established infrastructure for pandemic preparedness, with existing, sustainable platforms ready to be activated. This includes platforms for disease surveillance, virus circulation, and vaccine performance monitoring based on Real-World data, to complement clinical trial evidence. Areas covered Because of its complexity, this can best be done by combining efforts between public and private sectors, developing a multi-stakeholder approach. Public-Private-Partnerships increasingly play a critical role in combating infectious diseases but are still looked at with hesitancy. The Development of Robust and Innovative Vaccine Effectiveness (DRIVE) project, which established a platform for measuring brand-specific influenza vaccine effectiveness in Europe, exemplifies how to build a collaborative platform with transparent governance, state-of-the-art methodology, and a large network of participating sites. Lessons learned from DRIVE have been cardinal to set up COVIDRIVE, a platform for brand-specific COVID-19 vaccine effectiveness monitoring. Expert opinion The DRIVE partners propose that a debate on the benefits of Public-Private-Partnership-generated real-world evidence for vaccine effectiveness monitoring should be pursued to clarify roles and responsibilities, set up expectations, and decide the future environment for vaccine monitoring in Europe. In parallel, the driving factors behind PPP hesitancy should be studied.

An experience of scaling and intensifying the industrial production of the Gam-COVID-Vac vector adenovirus vaccine in the limiting conditions of the pandemic

The COVID-19 pandemic has presented a global challenge to the health system. More than 200 years of world epidemiological experience since the first mass use of vaccines have convincingly shown that effective vaccines are the key tools in the fight against dangerous infectious diseases, especially epidemic and pandemic ones. In the context of a rapidly spreading pandemic of a new infectious agent, it is crucial not only to develop fundamentally new vaccines, but also to be able to quickly organise their large-scale production. In the Russian Federation, in 2020, a team of the National Research Centre for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya developed an innovative vector vaccine, Gam-COVID-Vaс, for the prevention of coronavirus disease caused by the SARS-CoV-2 virus. A number of pharmaceutical companies faced the challenge of producing the vaccine. The aim of the study was to optimise the production technology of Gam-COVID-Vac for scaling and increasing the production capacity. In the course of the work, the authors established critical quality attributes of the product, optimised analytical methods for their control, identified poorly scalable technological stages, streamlined the technological process before its transfer to production, and modified non-scalable and technologically unfeasible stages. The work resulted in the launch of industrial-scale production of active pharmaceutical ingredients for both components of Gam-COVID-Vac, which made it possible not only to meet the critical need for COVID-19 immunoprophylaxis in the Russian Federation, but also to supply this vaccine to a number of foreign countries.

Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments.

This review is an update of an earlier narrative review published in 2015 on developments in the clinical management of cutaneous leishmaniasis (CL) including diagnosis, treatment, prevention and control measurements. CL is a vector-borne infection caused by the protozoan parasite Leishmania. The vector is the female sandfly. Globally, CL affects 12 million cases and annually 2 million new cases occur. CL is endemic in almost 100 countries and the total risk population is approximately 350 million people. WHO lists CL an emerging and uncontrolled disease and a neglected tropical disease. Local experience-based evidence remains the mainstay for the management of CL. Whereas intralesional therapeutic options are the first treatment option for most CL patients, those with mucocutaneous and disseminated involvement require a systemic therapeutic approach. Moreover, different Leishmania species can vary in their treatment outcomes. Therefore, species determination is critical for optimal CL clinical management. New DNA techniques allow for relatively easy Leishmania species determination, yet they are not easily implemented in resource-limited settings. There is a desperate need for novel, less toxic, and less painful treatment options, especially for children with CL. Yet, the large and well conducted studies required to provide the necessary evidence are lacking. To further control and potentially eliminate CL, we urgently need to improve vector control, and diagnostics, and we require efficient and safe vaccines. Alas, since CL primarily affects poor people, biotechnical companies dedicate little investment into the research programs that could lead to diagnostic, pharmaceutical, and vaccine innovations.

Immunological Examination of Echinococcus granulosus as a Candidate for Cancer Treatment and Vaccine Development: A Review Study

Echinococcus granulosus, is a cestode parasite that causes cystic echinococcosis. The vaccination procedure with tumor-associated antigens, coming from evolutionary distant organisms such as parasites, can be beneficial to override tolerance problems encountered with human tumor-associated antigens-based cancer therapeutic approaches. In this article, different databases of PubMed, Google Scholar, IranDoc and SID were examined from 2001 to 2021 and related articles were investigated. The review of related studies concerning human beings' treatment revealed the possibility of inhibition of cancer development via HCF antigens and mucin peptides extracted from this cestode. Besides, HCF treatment in animal models mostly showed that anti-cancer immune responses were activated. Of note, an influential issue in the design process of an anti-cancer vaccine is triggering efficacious anti-tumor responses by using idyllic antigens for immunization against cancer. In this realm, many antigens have been studied for this purpose and showed different ranges of effectiveness. Based on the cross-reactivity among parasitic and tumor antigens, detection of parasitic antigens that are highly homologous with cancer antigens is an ideal objective for immunization against cancer cells. As the toxicity of HCF was reported in some studies, further research are required to shed light on finding an innovative anti-cancer vaccine derived from parasites. This review article is useful for health managers and researchers working on the anti-cancer vaccine development.

Multi-Strain Human Papillomavirus (HPV) Vaccine Innovation via Computational Study: A Mini Review

Human papillomavirus (HPV) is a small and non-enveloped deoxyribonucleic acid (DNA) virus that infected mucosal cells. This viral genome is composed of early and late genes. Late (L) encodes the L1 and L2 proteins. The structural protein L1 is located outside the virion. It contributes to the viral attachment mechanism; hence it becomes the target for multi-strain vaccine design. This review aims to discuss the potency of conserved L1 HPV region and the innovation of multi-strain vaccines for prevention strategies of HPV infection. Bioinformatics methods in vaccine design applied for identification of conserved sequences from databases, epitopes map, antigenicity test, prediction of similarity, and autoimmune level. The multi-strain vaccine innovation initiated in this review has more benefits compared to previous vaccines based on the level of vaccine coverage via conserved regions, potential of immune cell epitopes, antigenic properties, and possibility of autoimmune when produced. Therefore, the multi-strain HPV vaccines are predicted to be more effective than previous vaccines, including bivalent or quadrivalent. In conclusion, the strategy for expanding the prevention of HPV infection could be carried out by developing a new multi-strain-based vaccine by using conserved regions in L1 capsid from all virus strains to increase the protection.

Neglected Tropical Diseases of Public Health Importance in India: Current Status and the Way Ahead

Introduction: In global health, critical challenges have erupted from infectious diseases, including the emergence and re-emergence of old and new infectious diseases. This is directly attributed to rapid human development including massive demographic changes, increasing population, and environmental degradation to name a few. Despite tremendous advances in the health of its citizens who live below the poverty line, India bears a disproportionately high burden of neglected tropical diseases with over half of the 20 WHO classified neglected tropical diseases at endemic levels. In a global fight against these diseases, India occupies a unique place as a country that despite being deeply affected by these devastating and deadly illnesses, also holds solutions on how innovation might eliminate these ancient maladies.
 Aims and Objectives: The present article reviews the common neglected tropical diseases of India, their magnitude and current status with respect to interventions for their control, challenges in the path of their elimination and the comprehensive all-inclusive approaches that can be adopted to curb the tropical disease burden of the Indian sub-continent.
 Methodology: The present study is literature review. PubMed, EMBASE and Scopus databases were searched using the key words “ neglected tropical diseases”, “infectious diseases”, “treatment of tropical diseases” and their MeSH terms in any possible combination using the logical operators “AND” and “OR”. The reference list of all the studies was screened to identify other studies of interest. The search was reiterated until July 2021.
 Results: Though the progress towards elimination of neglected tropical diseases is already underway, a concerted strategy is needed to assist the elimination efforts for these diseases. An all-inclusive policy to foster research and innovation in drug discovery, diagnostics, and vaccine development in neglected tropical diseases is lacking. There is also an absence of structured training of healthcare workers to improve their skills and capacity in disease management in endemic and disease prone areas.
 Conclusion: To obtain the high objective of improving health and reducing vulnerabilities, it is important that healthcare workers and professionals from other backgrounds bind together to broaden the perspectives that are needed to address. There is a call for a comprehensive policy for neglected diseases research in India to foster drugs, diagnostics, and vaccine innovation, critical for evolving needs for elimination programs.

Responding to a disease with resources from other diseases: Evidence from Zika vaccine research dynamics

AbstractResponding to health needs in one disease area might rely on being able to draw on research and funding oriented towards other disease areas. However, the tendency of medical research to cross-disease areas has received limited empirical consideration. An outbreak, in a disease area with little prior research or funding, means that any research response will necessarily be rich with cross-disease flows. This affords a setting that allows us to identify and examine the phenomenon over time. We estimate the extent to which the vaccine research community’s response to Zika virus drew on research and funding from other diseases. We find that a persistently low share of funding into Zika vaccine research was Zika-oriented. In contrast, a much higher share of knowledge inputs was oriented to Zika. The exercise serves to illustrate some general themes in priority setting for health research systems alongside some core features of vaccine innovation.

Path Forward to Optimise Post-approval Change Management and Facilitate Continuous Supply of Medicines and Vaccines of High Quality Worldwide

Post-approval changes (PACs) to the registered information of authorised medicinal products are introduced routinely worldwide to enhance the robustness and efficiency of the manufacturing process, ensure timely supply in case of increased demand, improve quality control techniques, respond to changes in regulatory requirements and upgrade to state-of-the-art facilities. These are critical to prevent supply disruption and continuously improve existing medicines and vaccines. Due to the complexity of current PAC systems across markets, a change can take 3 to 5 years to approval globally (Hoath et al in BioProcess Int, 2016) thus hindering innovation and increasing the risk of shortages. The key messages are as follows: 1. Industry believes that global regulatory convergence of post-approval changes to Marketing Authorisations (MAs) using science- and risk-based approaches will enable a more efficient management of quality and supply improvements and will facilitate patients’ access to innovative medicines and vaccines of the highest quality. 2. National Regulatory Authorities (NRAs) should establish national or regional guidelines in line with international standards (regarding a risk-based classification of changes and standardisation of requirements) (Guidelines on procedures and data requirements for changes to approved biotherapeutic products, in WHO Technical Report Series, 2018, Guidelines on procedures and data requirements for changes to approved vaccines, in WHO Technical Report Series, 2015), have clear procedural guidance including timelines and implement reliance pathways to accelerate the approval of changes. This paper briefly outlines the challenges for PACs and provides solutions for a more flexible and aligned global system.

Basic and Applied Sciences: Technology and Immunobiological Products.

The experience in organizing the creation of innovative immunobiological drugs and vaccines is discussed—from laboratory developments to industrial technologies and the registration of finished forms of effective and safe drugs that are in demand in the domestic and foreign markets. The principles of their action rely on the latest global achievements in the field of immunobiology and vaccinology.

Progress towards the Development of a Universal Influenza Vaccine.

Influenza viruses are responsible for millions of cases globally and significantly threaten public health. Since pandemic and zoonotic influenza viruses have emerged in the last 20 years and some of the viruses have resulted in high mortality in humans, a universal influenza vaccine is needed to provide comprehensive protection against a wide range of influenza viruses. Current seasonal influenza vaccines provide strain-specific protection and are less effective against mismatched strains. The rapid antigenic drift and shift in influenza viruses resulted in time-consuming surveillance and uncertainty in the vaccine protection efficacy. Most recent universal influenza vaccine studies target the conserved antigen domains of the viral surface glycoproteins and internal proteins to provide broader protection. Following the development of advanced vaccine technologies, several innovative strategies and vaccine platforms are being explored to generate robust cross-protective immunity. This review provides the latest progress in the development of universal influenza vaccines.

Comparative characterization of antibody responses induced by Ad5-vectored spike proteins of emerging SARS-CoV-2 VOCs

Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world, and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic. Here, we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern (VOCs). Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects, and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants. In contrast, prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants. The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs. In particular, the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies; moreover, with prime-boost regimens, this vaccine elicited an optimal specific neutralizing antibody response to Omicron, and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster. Overall, this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.

Preclinical study of immunogenicity of adjuvanted quadrivalent subunit influenza vaccine

Background. Preventive vaccination is a vitally important strategic aspect of protection of the population against severe effects of influenza epidemics. The priority attention is given to development of effective tetravalent vaccines containing antigens of two influenza A lineages (H1N1, H3N2) and two influenza B lineages (Victoria and Yamagata) in combination with immunoadjuvants.The aim of the work was to conduct the preclinical study of the immunogenicity and protective efficacy of the innovative tetravalent subunit vaccine containing antigens of influenza A and B viruses as well as a corpuscular adjuvant.Materials and methods. The study was conducted using female BALB/c mice. The tetravalent vaccine and monovalent intermediate vaccines combined with a betulin adjuvant were injected intraperitoneally two times at a 14-day interval. The immunogenic activity was measured by the hemagglutination inhibition assay. The protective activity of the vaccine was assessed by changes in the viral load, body weight and survival rates using the mouse model of fatal influenza A H1N1 virus infection.Results. The mice vaccinated with the adjuvanted quadrivalent subunit influenza vaccine produced antibodies against all four influenza viruses included in the vaccine; the mean antibody titers in the hemagglutination inhibition assay were above 1 : 40. The second-dose vaccination induced a significant increase in levels of antibodies against all four influenza viruses. The dose of the quadrivalent subunit adjuvanted vaccine containing 5 µg of each antigen and 200 µg of the adjuvant provided a 100% survival rate in mice and significantly decreased lung viral titers (more than 3 lg TCID50) in the mouse model of influenza pneumonia.Conclusion. The quadrivalent subunit vaccine with the betulin-based corpuscular adjuvant demonstrates high immunogenicity in laboratory mice and provides protection against fatal pneumonia caused by the influenza A virus subtype H1N1.

DNA-Vaccine-Induced Immune Response Correlates with Lower Viral SARS-CoV-2 Titers in a Ferret Model.

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral circulation, with a significant number of deaths. To further explore alternative vaccination platforms, we developed COVID-eVax—a genetic vaccine based on plasmid DNA encoding the RBD domain of the SARS-CoV-2 spike protein. Here, we describe the correlation between immune responses and the evolution of viral infection in ferrets infected with the live virus. We demonstrate COVID-eVax immunogenicity as means of antibody response and, above all, a significant T-cell response, thus proving the critical role of T-cell immunity, in addition to the neutralizing antibody activity, in controlling viral spread.