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Background Inhaled recombinant COVID-19 vaccine (type 5 adenoviral vector) (hereinafter referred to as the inhaled COVID-19 vaccine) is the first approved inhaled COVID-19 vaccine in China, with the advantages of good immunity, painlessness, and higher accessibility, which has been included in the WHO Emergency Use Listing and China's list of second-dose booster immunization vaccines. The real-world application of this vaccine deserves more attention due to the poor understanding of it by the public. Objective To understand the real experience in depth of first-line medical staff in epidemic prevention aged≥18 years in Guiyang city who received inhaled COVID-19 vaccine, so as to provide a reference for the promotion of this type of vaccine. Methods The recipients who completed the emergency vaccination with inhaled COVID-19 vaccine at a vaccination site of Guiyang city in October 2022 were selected as research subjects based on the the principle of booster immunization by using purposive sampling method. The sample size was determined by interviewing until no new case emerged which was data saturation. A total of 17 recipients were interviewed in this study. Semi-structured interviews were conducted with the research subjects, face-to-face interviews were conducted to understand the vaccination experience at that time firstly, and telephone interviews were conducted 5-7 days after vaccination. The Colaizzi seven-step analysis method was used for the data collection and analysis. Results A total of five themes were summarized including the convenience of vaccination, good vaccination experience, light psychological burden, low vaccine hesitancy and uncertain protective effect. The convenience of vaccination includes simple and time-saving vaccination process, fast vaccination speed, low cost, and no interruption of nucleic acid testing; the good vaccination experience includes comfortable feeling of vaccination, harmonious observation atmosphere, fewer adverse reactions, and no interference with daily life; light psychological burden includes reduction of tension and anxiety of vaccination, better mental health maintenance, non-invasive vaccination and elimination of vaccination fears; low vaccine hesitancy includes high vaccination accessibility, increase of vaccine acceptance, increase of public perception of epidemic outbreak risk; uncertain protective effect includes uncertain which vaccination method provides better protection between injection and inhalation, whether inhaled COVID-19 vaccine has a good protective effect against variant strains. Conclusion Inhaled COVID-19 vaccine is convenient to administer with fewer adverse reactions, which is highly accepted by first-line medical staff in epidemic prevention aged≥18 years in Guiyang city with good experience.

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge. [ABSTRACT FROM AUTHOR]

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6–125.0) vs. 51.0 (17.9–122.3), p = 0.024), 2–3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5–926.5) vs. 555.0 (287.3–926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5–655.3) vs. 176.0 (94.3–255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed. [ABSTRACT FROM AUTHOR]

Vaccines against parasites have lagged centuries behind those against viral and bacterial infections, despite the devastating morbidity and widespread effects of parasitic diseases across the globe. One of the greatest hurdles to parasite vaccine development has been the lack of vaccine strategies able to elicit the complex and multifaceted immune responses needed to abrogate parasitic persistence. Viral vectors, especially adenovirus (AdV) vectors, have emerged as a potential solution for complex disease targets, including HIV, tuberculosis, and parasitic diseases, to name a few. AdVs are highly immunogenic and are uniquely able to drive CD8+ T cell responses, which are known to be correlates of immunity in infections with most protozoan and some helminthic parasites. This review presents recent developments in AdV-vectored vaccines targeting five major human parasitic diseases: malaria, Chagas disease, schistosomiasis, leishmaniasis, and toxoplasmosis. Many AdV-vectored vaccines have been developed for these diseases, utilizing a wide variety of vectors, antigens, and modes of delivery. AdV-vectored vaccines are a promising approach for the historically challenging target of human parasitic diseases. [ABSTRACT FROM AUTHOR]

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge.

With emergent Sars-Cov-2, a highly transmissive virus that caused millions of deaths worldwide, the development of vaccines became urgent to combat COVID-19. Although rare, important adverse effects had been described in a hypothetical scenario of immune system overstimulation or overreaction. Still’s disease is a rare inflammatory syndrome of unknown etiology. It manifests as a cytokine storm, mainly IL-18 and IL-1β, and presents itself with fever spikes, joint pain, maculopapular evanescent salmon-pink skin rash, and sore throat, among other symptoms. Here, we report a case of a 44-year-old healthy male who developed adult-onset Still’s disease (AOSD) with atypical symptoms after both doses of ChAdOx1 nCoV-19 vaccine with 3 months of dose interval. The medical team suspected Still's disease and started prednisone 1 mg/kg (40mg). The next day the patient showed a marked improvement in articular and chest pains and had no other fever episodes. Therefore, he was discharged to continue the treatment in outpatient care. On the six-month follow-up, the patient was free of complaints, and the progressive corticoid withdrawal plan was already finished.

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6–125.0) vs. 51.0 (17.9–122.3), p = 0.024), 2–3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5–926.5) vs. 555.0 (287.3–926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5–655.3) vs. 176.0 (94.3–255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.

In the new science emanating from the COVID-19 pandemic, effective vaccine development has made a huge difference and saved countless lives. Vaccine roll-out led to the identification of rare cases of severe thrombotic and thrombocytopenic problems in some recipients. This apparent coupling of thrombosis with haemorrhagic potentiation might seem baffling but the ensuing clinical investigation rapidly shed important light on its molecular mechanism. This review outlines the current understanding on the role of adenovirus-based platforms, the immunogenic triggers and the immunothrombotic response underlying vaccine-induced immune thrombotic thrombocytopenia. [ABSTRACT FROM AUTHOR]

Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10-8-10-6 M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10-7-10-4 M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of magnitude lower concentrations. PEG and sucrose maintained immunogenicity in vivo for viruses stored for 10 days at 37 °C. To achieve rational design of viral-vaccine stabilizers, our approach is aided by simplified quantitative models based on a single rate-limiting step.

Vaccines against parasites have lagged centuries behind those against viral and bacterial infections, despite the devastating morbidity and widespread effects of parasitic diseases across the globe. One of the greatest hurdles to parasite vaccine development has been the lack of vaccine strategies able to elicit the complex and multifaceted immune responses needed to abrogate parasitic persistence. Viral vectors, especially adenovirus (AdV) vectors, have emerged as a potential solution for complex disease targets, including HIV, tuberculosis, and parasitic diseases, to name a few. AdVs are highly immunogenic and are uniquely able to drive CD8+ T cell responses, which are known to be correlates of immunity in infections with most protozoan and some helminthic parasites. This review presents recent developments in AdV-vectored vaccines targeting five major human parasitic diseases: malaria, Chagas disease, schistosomiasis, leishmaniasis, and toxoplasmosis. Many AdV-vectored vaccines have been developed for these diseases, utilizing a wide variety of vectors, antigens, and modes of delivery. AdV-vectored vaccines are a promising approach for the historically challenging target of human parasitic diseases.

On March 13, 2021, Tunisia started a widespread immunization program against SARS-CoV-2 utilizing different vaccinations that had been given emergency approval. Herein, we followed prospectively a cohort of participant who received COVID-19 vaccine (Pfizer BioNTech and Sputnik-Gameleya V). The goal of this follow-up was to define the humoral and cellular immunological profile after immunization by assessing neutralizing antibodies and IFN- γ release. 26 vaccinated health care workers by Pfizer BioNTech (n=12) and Sputnik-Gameleya V (n=14) were enrolled from June to December 2021 in Military hospital of Tunis. All consenting participants were sampled for peripheral blood after three weeks of vaccination. The humoral response was investigated by the titer of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies to S1 protein. The CD4 and CD8 T cell responses were evaluated by the QuantiFERON® SARS-CoV-2 (Qiagen® Basel, Switzerland). Regardless the type of vaccine, the assessment of humoral and cellular response following vaccination showed a strong involvement of the later with expression of IFN-γ as compared to antibodies secretion. Moreover, we showed that people with past SARS-CoV-2 infection developed high levels of antibodies than those who are not previously infected. However, no significant difference was detected concerning interferon gamma (IFN-γ) expression by CD4 and CD8 T cells in health care worker (HCW) previously infection or not with COVID-19 infection. Analysis of immune response according to the type of vaccine, we found that Pfizer BioNTech induced high level of humoral response (91.66%) followed by Sputnik-Gameleya V (64.28%). However, adenovirus vaccine gave a better cellular response (57.14%) than mRNA vaccine (41.66%). Regarding the immune response following vaccine doses, we revealed a significant increase of neutralizing antibodies and IFN-γ release by T cells in patients fully vaccinated as compared to those who have received just one vaccine. Collectively, our data revealed a similar immune response between Pfizer BioNTech and Sputnik-Gameleya V vaccine with a slight increase of humoral response by mRNA vaccine and cellular response by adenovirus vaccine. It's evident that past SARS-CoV-2 infection was a factor that contributed to the vaccination's increased immunogenicity. However, the administration of full doses of vaccines (Pfizer BioNTech or Sputnik-Gameleya V) induces better humoral and cellular responses detectable even more than three months following vaccination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

In recent years, multivariate data analysis (MVDA) has been widely used for process characterization and fault diagnosis in the biopharmaceutical industry. This study aims to investigate the feasibility of using MVDA for the development and scale-up of a perfusion process for HEK293 cell-based recombinant adenovirus zoster vaccine (Ad-HER) production. The Principal Component Analysis (PCA) results suggested comparable performance among the ATF, PATFP, and BFP perfusion systems in benchtop-scale stirred-tank bioreactor (STR). Then a Batch Evolution Model (BEM) was built using representative data from 10 L STR with a BFP system to assess the Ad-HER perfusion process performance at pilot-scale bioreactor (50 L STR and 50 L wave bioreactor). Furthermore, another BEM model and Batch Level Model (BLM) were built to monitor process parameters over time and predict the final adenovirus titer in 50 L wave bioreactor. The loading plot revealed that lactate dehydrogenase activity, viable cell diameter, and base-added during the virus production phase could be used as preliminary indicators of adenovirus yield. Finally, an adenovirus titer of 2.0±0.3×10 10 IFU/mL was achieved in the 50 L wave bioreactor with BFP system, highlighting the robustness of the Ad-HER perfusion process at pilot-scale. Overall, this study emphasizes the effectiveness of MVDA as a tool for advancing the understanding of recombinant adenovirus vaccine perfusion production process development and scale-up., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Non-replicating adenovirus-based vectors have been broadly used for the development of prophylactic vaccines in humans and are licensed for COVID-19 and Ebola virus disease prevention. Adenovirus-based vectored vaccines encode for one or more disease specific transgenes with the aim to induce protective immunity against the target disease. The magnitude and duration of transgene expression of adenovirus 5- based vectors (human type C) in the host are key factors influencing antigen presentation and adaptive immune responses. Here we characterize the magnitude, duration, and organ biodistribution of transgene expression after single intramuscular administration of adenovirus 26-based vector vaccines in mice and evaluate the differences with adenovirus 5-based vector vaccine to understand if this is universally applicable across serotypes. We demonstrate a correlation between peak transgene expression early after adenovirus 26-based vaccination and transgene-specific cellular and humoral immune responses for a model antigen and SARS-CoV-2 spike protein, independent of innate immune activation. Notably, the memory immune response was similar in mice immunized with adenovirus 26-based vaccine and adenovirus 5-based vaccine, despite the latter inducing a higher peak of transgene expression early after immunization and a longer duration of transgene expression. Together these results provide further insights into the mode of action of adenovirus 26-based vector vaccines., Competing Interests: The authors declare the following competing interests: all authors are or were employees of Janssen Vaccines & Prevention B.V while engaged in the research project. N.C.S., J.S., S.K. and R.C.Z. held or hold stock in Johnson & Johnson. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Marquez-Martinez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Influenza virus is a kind of virus that poses several hazards of animal and human health. Therefore, it is important to develop an effective vaccine to prevent influenza. To this end we successfully packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP. The effect of rAd-NP-M2e-GFP on the activation of dendritic cell (DC) in vitro and in vivo was detected by intranasal immunization. The results showed that rAd-NP-M2e-GFP promoted the activation of DC in vitro and in vivo. After the primary immunization and booster immunization of mice through the nasal immune way, the results showed that rAd-NP-M2e-GFP induced enhanced local mucosal-specific T cell responses, increased the content of SIgA in broncho alveolar lavage fluids (BALF) and triggered the differentiation of B cells in the germinal center. It is proved that rAd-NP-M2e-GFP can significantly elicit mucosal immunity and systemic immune response. In addition, rAd-NP-M2e-GFP could effectively protect mice after H1N1 influenza virus challenge. To lay the foundation and provide reference for further development of influenza virus mucosal vaccine in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Feline coronavirus (FCoV) is an unsegmented, single-stranded RNA virus belonging to the Alphacoronavirus genus. It can cause fatal feline infectious peritonitis (FIP) in cats of any ages. Currently, there are no effective prevention and control measures to against FCoV. In this study, we developed a recombinant adenovirus vaccine, AD5-N, based on the nucleocapsid(N) protein of FCoV. The immunogenicity of AD5-N was evaluated through intramuscular immunization in 6-week-old Balb/c mice and 9-12 months old cats. Compared to the control group, AD5-N specifically induced a significant increase in IgG and SIgA levels in the vaccinated mice. Furthermore, AD5-N not only effectively promoted strong cellular immune responses in cats but also induced high levels of specific SIgA, effectively helping cats resist FCoV infection. Our findings suggest that adenovirus vector vaccines based on the N gene have the potential to become candidate vaccines for the prevention and control of FCoV infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Small laboratory animals are powerful models for investigating in vivo viral pathogenesis of a number of viruses. For adenoviruses (AdVs), however, species‐specificity poses limitations to studying human adenoviruses (HAdVs) in mice and other small laboratory animals. Thus, this review covers work on naturally occurring mouse AdVs, primarily mouse adenovirus type 1 (MAdV‐1), a member of the species Murine mastadenovirus A. Molecular genetics, virus life cycle, cell and tissue tropism, interactions with the host immune response, persistence, and host genetics of susceptibility are described. A brief discussion of MAdV‐2 (member of species Murine mastadenovirus B) and MAdV‐3 (member of species Murine mastadenovirus C) is included. We report the use of MAdVs in the development of vectors and vaccines. [ABSTRACT FROM AUTHOR]

Among students with influenza-like illness at a Pennsylvania college student health center during 2016–2017, 44 (15%) of 288 with respiratory specimens tested positive for human adenovirus (HAdV). HAdV-3, -7, and -4 predominated, and types clustered temporally. HAdV infection should be considered among college students with acute respiratory illness.

We estimated the risk of death from coronavirus disease 2019 in vaccinated compared with unvaccinated patients. The risk of death was reduced 44% after 1 dose of the Pfizer-BioNTech BNT162b2 vaccine, 55% after 1 dose of the Oxford-Astrazeneca ChAdOx1 vaccine, and 69% after 2 doses of the BNT162b2 vaccine. This is above the protection provided against infection., Competing Interests: Potential conflicts of interest. M. R. reports funding from the UK National Institute for Health Research/Vaccine Task Force (grant NIHR203292; funding for COV-BOOST trial under contract via University Hospital Southampton NHS Foundation Trust), during the conduct of the study. M. R. also reports that the Immunisation Department has provided vaccine manufacturers with postmarketing surveillance reports on pneumococcal and meningococcal infection, which the companies are required to submit to the UK Licensing authority in compliance with their risk management strategy; a cost recovery charge is made for these reports (nonfinancial support from Pfizer/GSK). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31-61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. KEY POINTS: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice., (© 2024. The Author(s).)

The Coalition for Epidemic Preparedness Innovations' "100-day moonshot" aspires to launch a new vaccine within 100 days of pathogen identification, followed by large-scale vaccine availability within the "second hundred days." Here, we describe work to optimize adenoviral vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing output from the available manufacturing footprint. We describe a rapid virus seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by approximately fourfold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10,000 doses from each liter of bioreactor capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response., (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Herpes zoster (HZ) results from waning immunity following childhood infection with varicella zoster virus (VZV) but is preventable by vaccination with recombinant HZ vaccine or live HZ vaccine (two doses or one dose, respectively). Vaccine efficacy declines with age, live HZ vaccine is contraindicated in immunosuppressed individuals, and severe local reactogenicity of recombinant HZ vaccine is seen in up to 20% of older adults, indicating a potential need for new vaccines. Nonreplicating chimpanzee adenovirus (ChAd) vectors combine potent immunogenicity with well-established reactogenicity and safety profiles. We evaluated the cellular and humoral immunogenicity of ChAdOx1 encoding VZV envelope glycoprotein E (ChAdOx1-VZVgE) in mice using IFN-γ ELISpot, flow cytometry with intracellular cytokine staining, and ELISA. In outbred CD-1 mice, one dose of ChAdOx1-VZVgE (1 × 10 7 infectious units) elicited higher gE-specific T cell responses than two doses of recombinant HZ vaccine (1 µg) or one dose of live HZ vaccine (1.3 × 10 3 plaque-forming units). Antibody responses were higher with two doses of recombinant HZ vaccine than with two doses of ChAdOx1-VZVgE or one dose of live HZ vaccine. ChAdOx1-VZVgE boosted T cell and antibody responses following live HZ vaccine priming. The frequencies of polyfunctional CD4+ and CD8+ T cells expressing more than one cytokine (IFN-γ, TNF-α and IL-2) were higher with ChAdOx1-VZVgE than with the conventional vaccines. Results were similar in young and aged BALB/c mice. These findings support the clinical development of ChAdOx1-VZVgE for prevention of HZ in adults aged 50 years or over, including those who have already received conventional vaccines.

Human adenovirus (HAdV), particularly the HAdV type 5 (HAdV-5), has been extensively utilized in the development of vector vaccines due to its high immunogenicity, good safety profile, and ease of propagation. However, one of the main challenges in its use is the presence of pre-existing immunity among vaccine recipients. Pre-existing neutralizing antibodies (NAbs) can prevent the uptake of HAdV-5 vectors and reduce vaccine efficacy. Hence, this study investigated the seroprevalence of NAbs against HAdV-5 in urban and rural regions of the Philippines. Luciferase-based neutralization assay was performed on 391 plasma/serum samples. Out of these samples, 346 or 88.5% were positive for HAdV-5 NAbs, and the majority of them (56.8%) had high titers against the virus. Among the regions included in this study, Bicol (Region V) had the highest seroprevalence rate (94.1%). Our findings show that a significant number of adults in the Philippines have pre-existing immunity against HAdV-5. This supports the recommendation that vaccination programs in the country should consider implementing vaccination techniques, such as a prime-boost regimen or addition of booster doses, to address the potential negative effects of pre-existing HAdV-5 immunity in the efficacy of adenoviral vector-based vaccines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Francisco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and efficacious vaccine is urgently required to prevent and control the disease. In this study, we evaluated the safety and immunogenicity of replication-incompetent type-2 adenoviruses carrying African swine fever virus (ASFV) antigens, namely CP204L (p30), E183L (p54), EP402R (CD2v), B646L (p72), and B602L (p72 chaperone). A vaccine cocktail delivered by simultaneous intramuscular (IM) and intranasal (IN) administration robustly elicited both systemic and mucosal immune responses against AFSV in mice and swine and provided highly effective protection against the circulating ASFV strain in farmed pigs. This multi-antigen cocktail vaccine was well tolerated in the vaccinated animals. No significant interference among antigens was observed. The combined IM and IN vaccination using this adenovirus-vectored antigen cocktail vaccine warrants further evaluation for providing safe and effective protection against ASFV infection and transmission.

The major immunogenic protein capsid (Cap) of porcine circovirus type 2 (PCV2) is critical to induce neutralizing antibodies and protective immune response against PCV2 infection. This study was conducted to investigate the immune response of recombinant adenovirus expressing PCV2b Cap and C-terminal domain of Yersinia pseudotuberculosis invasin (Cap-InvC) fusion protein in pigs. The recombinant adenovirus rAd-Cap-InvC, rAd-Cap and rAd were generated and used to immunize pigs. The phosphate-buffered saline was used as negative control. The specific antibodies levels in rAd-Cap-InvC and ZJ/C-strain vaccine groups were higher than that of rAd-Cap group (p < 0.05), and the neutralization antibody titer in rAd- Cap-InvC group was significantly higher than those of other groups during 21-42 days postimmunization (DPI). Moreover, lymphocyte proliferative level, interferon-γ and interleukin-13 levels in rAd-Cap-InvC group were increased compared to rAd-Cap group (p < 0.05). After virulent challenge, viruses were not detected from the blood samples in rAd-Cap-InvC and ZJ/C-strain vaccine groups after 49 DPI. And the respiratory symptom, rectal temperature, lung lesion and lymph node lesion were minimal and similar in the ZJ/C-strain and rAd-Cap- InVC groups. In conclusion, our results demonstrated that rAd-Cap-InvC was more efficiently to stimulate the production of antibody and protect pigs from PCV2 infection. We inferred that InvC is a good candidate gene for further development and application of PCV2 genetic engineering vaccine. [ABSTRACT FROM AUTHOR]

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes severe watery diarrhea, vomiting, dehydration and high mortality in piglets, resulting in significant economic losses by the global pig industry. Recently, PDCoV has also shown the potential for cross-species transmission. However, there are currently few vaccine studies and no commercially available vaccines for PDCoV. Hence, here, two novel human adenovirus 5 (Ad5)-vectored vaccines expressing codon-optimized forms of the PDCoV spike (S) glycoprotein (Ad-PD-tPA-Sopt) and S1 glycoprotein (Ad-PD-oriSIP-S1opt) were constructed, and their effects were evaluated via intramuscular (IM) injection in BALB/c mice with different doses and times. Both vaccines elicited robust humoral and cellular immune responses; moreover, Ad-PD-tPA-Sopt-vaccinated mice after two IM injections with 10 8 infectious units (IFU)/mouse had significantly higher anti-PDCoV-specific neutralizing antibody titers. In contrast, the mice immunized with Ad-PD-tPA-Sopt via oral gavage (OG) did not generate robust systemic and mucosal immunity. Thus, IM Ad-PD-tPA-Sopt administration is a promising strategy against PDCoV and provides useful information for future animal vaccine development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

To contain the spread of the SARS-CoV-2 pandemic, rapid development of vaccines was required in 2020. Rational design, international efforts, and a lot of hard work yielded the market approval of novel SARS-CoV-2 vaccines based on diverse platforms such as mRNA or adenovirus vectors. The great success of these technologies, in fact, contributed significantly to control the pandemic. Consequently, most scientific literature available in the public domain discloses the results of clinical trials and reveals data of efficaciousness. However, a description of processes and rationales that led to specific vaccine design is only partially available, in particular for adenovirus vectors, even though it could prove helpful for future developments. Here, we disclose our insights from the endeavors to design compatible functional adenoviral vector platform expression cassettes for the SARS-CoV-2 spike protein. We observed that contextualizing genes from an ssRNA virus into a DNA virus provides significant challenges. Besides affecting physical titers, expression cassette design of adenoviral vaccine candidates can affect viral propagation and spike protein expression. Splicing of mRNAs was affected, and fusogenicity of the spike protein in ACE2-overexpressing cells was enhanced when the ER retention signal was deleted.

As part of the COVID-19 vaccination campaign, the National Agency for the Safety of Medicines and Health Products and all 31 regional pharmacovigilance centers were mobilized in an exceptional reinforced vaccine pharmacovigilance surveillance system. Concerning adenovirus vaccines, Vaxzévria® and Jcovden®, this national system, based on the daily analysis of notified cases of adverse events, has allowed the early identification of safety signals, some of which have been validated, others still under analysis, common to mRNA vaccines or more specific of adenovirus vaccines such as Vaccine Induced Immune Thrombocytopenia. Complementing european and international actions, this follow-up has contributed to a better definition of the safety profile of these vaccines and has led to redefine the vaccine strategy in our country. Although today these two vaccines have no longer place in the national vaccine strategy, they are still used in other countries, where the experience acquired could be useful and will contribute to fuel the reflection on future therapies involving viral vectors., (Copyright © 2023 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites., Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival., Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed that animals vaccinated intranasally had improved cellular and mucosal antibody responses. Additionally, intranasally vaccinated animals had significantly better viremic control, and protection from lethal infection compared to intramuscularly vaccinated animals. Notably, in a novel transmission model, intranasal vaccination reduced viral transmission to naïve co-housed mice compared to intramuscular vaccination., Discussion: Our data provide convincing evidence for the use of intranasal vaccination in protecting against SARS-CoV-2 infection and transmission., Competing Interests: Authors JS, JZ, BG, and MR are employees of the company Altimmune Inc. and may have received stock options and other financial compensation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dickson, Geerling, Stone, Hassert, Steffen, Makkena, Smither, Schwetye, Zhang, Georges, Roberts, Suschak, Pinto and Brien.)

The ongoing COVID-19 pandemic caused by SARS-CoV-2 infection has threatened global health. Since the first case of infection was reported in December 2019, SARS-CoV-2 has rapidly spread worldwide and caused millions of deaths. As vaccination is the best way to protect the host from invading pathogens, several vaccines have been developed to prevent the infection of SARS-CoV-2, saving numerous lives thus far. However, SARS-CoV-2 constantly changes its antigens, resulting in escape from vaccine-induced protection, and the longevity of immunity induced by vaccines remains an issue. Additionally, traditional intramuscular COVID-19 vaccines are insufficient at evoking mucosal-specific immune responses. Because the respiratory tract is the primary route of SARS-CoV-2 entry, the need for mucosal vaccines is strong. Using an adenoviral (Ad) vector platform, we generated Ad5-S.Mod, a recombinant COVID-19 vaccine that encodes modified-spike (S) antigen and the genetic adjuvant human CXCL9. Intranasal delivery of Ad5-S.Mod elicited superior airway humoral and T-cell responses over traditional intramuscular vaccines and protected mice from lethal SARS-CoV-2 infection. cDC1 cells were required for the generation of antigen-specific CD8 + T-cell responses and CD8 + tissue-resident memory T-cell development in intranasal Ad5-S.Mod vaccinated mice. Furthermore, we confirmed the efficacy of the intranasal Ad5-S.Mod vaccine in terms of transcriptional changes and identified lung macrophages as a key supporter of maintenance of lung-resident memory T and B cells. Our study demonstrates Ad5-S.Mod has the potential to confer protective immunity against SARS-CoV-2 and that lung macrophages support the maintenance of vaccine-induced tissue-resident memory lymphocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of effective and flexible vaccine platforms is a major public health challenge, especially in the context of influenza vaccines that have to be renewed every year. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally, as demonstrated by the long-term use of oral AdV-4 and -7 vaccines in the U.S. military. These viruses therefore appear to be the ideal backbone for the development of oral replicating vector vaccines. However, research into these vaccines is limited by the ineffectiveness of human AdV replication in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicating conditions. Here, we orally vaccinated mice with a MAV-1 vector expressing influenza hemagglutinin (HA) to assess the protection conferred against an intranasal challenge of influenza. We showed that a single oral immunization with this vaccine generates influenza-specific and -neutralizing antibodies and completely protects mice against clinical signs and viral replication, similar to traditional inactivated vaccines. IMPORTANCE Given the constant threat of pandemics and the need for annual vaccination against influenza and possibly emerging agents such as SARS-CoV-2, new types of vaccines that are easier to administer and therefore more widely accepted are a critical public health need. Here, using a relevant animal model, we have shown that replicative oral AdV vaccine vectors can help make vaccination against major respiratory diseases more available, better accepted, and therefore more effective. These results could be of major importance in the coming years in the fight against seasonal or emerging respiratory diseases such as COVID-19., Competing Interests: The authors declare no conflict of interest.