Oral Vaccination Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 in a Syrian Hamster Challenge Model.

BACKGROUND: Vaccines that are shelf stable and easy to administer are crucial to improve vaccine access and reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission around the world. METHODS: In this study, we demonstrate that an oral, adenovirus-based vaccine candidate protects against SARS-CoV-2 in a Syrian hamster challenge model. RESULTS: Hamsters administered 2 doses of VXA-CoV2-1 showed a reduction in weight loss and lung pathology and had completely eliminated infectious virus 5 days postchallenge. Oral immunization induced antispike immunoglobulin G, and neutralizing antibodies were induced upon oral immunization with the sera, demonstrating neutralizing activity. CONCLUSIONS: Overall, these data demonstrate the ability of oral vaccine candidate VXA-CoV2-1 to provide protection against SARS-CoV-2 disease.

Comparative Evaluation of the Vaccine Efficacies of Three Adenovirus-Based Vector Types in the Friend Retrovirus Infection Model.

Adenovirus (AdV)-based vectors are popular experimental vaccine vectors, but despite their ability to induce strong immune responses, their application is impeded by widespread preexisting immunity against many AdV types that can impair or even abrogate the induction of transgene-specific immune responses. Therefore, the development of vectors based on AdV types with a low seroprevalence is important for effective AdV-based immunization in humans. We investigated the immunization efficacy of vectors based on AdV type 48 (Ad48) and Ad50 in the ovalbumin (ova) model as well as the Friend retrovirus (FV) model, which allows testing of the protective effect of vaccine-induced immunity. Using ova-encoding vectors, we found a significantly lower induction of ova-specific CD8+ T cells and antibody responses by Ad48- and Ad50-based vectors than by Ad5-based vectors. Similarly, we found a reduced induction of FV-specific CD8+ T cell responses in Ad48- and Ad50.Leader-Gag-immunized mice compared with that in Ad5-immunized mice; however, some of those mice were able to control the FV infection, and protection correlated with the level of neutralizing antibodies 10 days after FV challenge. Analyses of the AdV-specific antibodies and CD8+ T cells induced by the individual AdV types revealed a high level of cross-reactivity, and the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Our results show that the immunity induced by Ad48- and Ad50-based vectors is reduced compared to that induced by Ad5 and is sufficient to control FV infection in only some of the immunized mice. A high level of cross-reactivity suggests that AdV preimmunity must be considered even when applying rare AdV-based vectors.IMPORTANCE AdV-based vectors are important tools for the development of vaccines against a wide range of pathogens. While AdV vectors are generally considered safe and highly effective, their application can be severely impaired by preexisting immunity due to the widespread seroprevalence of some AdV types. The characterization of different AdV types with regard to immunogenicity and efficacy in challenge models is of great importance for the development of improved AdV-based vectors that allow for efficient immunization despite anti-AdV immunity. We show that the immunity induced by an Ad48-based vector is inferior to that induced by an Ad5-based vector but can still mediate the control of an FV infection in highly FV-susceptible mice. However, the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Importantly, we found cross-reactivity of both the humoral and cellular immune responses raised by the individual AdV types, suggesting that switching to a different AdV type may not be sufficient to circumvent preexisting anti-AdV immunity.

The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of sera in the immunized animals.

Viral pathogens have evolved a wide range of tactics to evade host immune responses and thus propagate effectively. One efficient tactic is to divert host immune responses toward an immunodominant decoy epitope and to induce non-neutralizing antibodies toward this epitope. Therefore, it is expected that the amount of decoy epitope in a subunit vaccine can affect the level of neutralizing antibody in an immunized animal. In this study, we tested this hypothesis by generating an antibody specific to the decoy epitope on the capsid protein of porcine circovirus type 2 (PCV2). Using this antibody, we found that two commercial vaccines contained statistically different amounts of the decoy epitope. The vaccine with lower levels of decoy epitope induced a significantly higher level of neutralizing antibody after immunization. This antibody can be used as an analytical tool to monitor the quality of a vaccine from batch to batch.

Vaccines for the common cold.

BACKGROUND: The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8º C). The widespread morbidity caused by the common cold worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. This is an update of a Cochrane review first published in 2011 and previously updated in 2013. OBJECTIVES: To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to September 2016), Embase (1974 to September 2016), CINAHL (1981 to September 2016), and LILACS (1982 to September 2016). We also searched three trials registers for ongoing studies and four websites for additional trials (February 2017). We included no language or date restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any virus vaccines compared with placebo to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated methodological quality and extracted trial data. We resolved disagreements by discussion or by consulting a third review author. MAIN RESULTS: We found no additional RCTs for inclusion in this update. This review includes one RCT dating from the 1960s with an overall high risk of bias. The RCT included 2307 healthy participants, all of whom were included in analyses. This trial compared the effect of an adenovirus vaccine against placebo. No statistically significant difference in common cold incidence was found: there were 13 (1.14%) events in 1139 participants in the vaccines group and 14 (1.19%) events in 1168 participants in the placebo group (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; P = 0.90). No adverse events related to the live vaccine were reported. The quality of the evidence was low due to limitations in methodological quality and a wide 95% confidence interval. AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with low-quality evidence. We found no conclusive results to support the use of vaccines for preventing the common cold in healthy people compared with placebo. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety, and mortality related to the vaccine.

Administration of Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and Avian Beta Defensin as Adjuvants in Inactivated Inclusion Body Hepatitis Virus and its Hexon Protein-Based Experimental Vaccine Formulations in Chickens.

Inclusion body hepatitis (IBH) is one of the major infectious diseases adversely affecting the poultry industry of the United States and Canada. Currently, no effective and safe vaccine is available for the control of IBH virus (IBHV) infection in chickens. However, based on the excellent safety and immunogenic profiles of experimental veterinary vaccines developed with the use of new generation adjuvants, we hypothesized that characterization of vaccine formulations containing inactivated IBHV or its capsid protein hexon as antigens, along with poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) and avian beta defensin 2 (ABD2) as vaccine adjuvants, will be helpful in development of an effective and safe vaccine formulation for IBH. Our data demonstrated that experimental administration of vaccine formulations containing inactivated IBHV and a mixture of PCEP with or without ABD2 as an adjuvant induced significantly higher antibody responses compared with other vaccine formulations, while hexon protein-based vaccine formulations showed relatively lower levels of antibody responses. Thus, a vaccine formulation containing inactivated IBHV with PCEP or a mixture of PCEP and ABD2 (with a reduced dosage of PCEP) as an adjuvant may serve as a potential vaccine candidate. However, in order to overcome the risks associated with whole virus inactivated vaccines, characterization of additional viral capsid proteins, including fiber protein and penton of IBHV along with hexon protein in combination with more new generation adjuvants, will be helpful in further improvements of vaccines against IBHV infection.

Dramatic decline of respiratory illness among US military recruits after the renewed use of adenovirus vaccines.

BACKGROUND: In late 2011, after a 12-year hiatus, oral vaccines against adenovirus types 4 (Ad4) and 7 (Ad7) were again produced and administered to US military recruits. This study examined the impact of the new adenovirus vaccines on febrile respiratory illness (FRI) and adenovirus rates and investigated if new serotypes emerged. FRI rates and their associated hospitalizations had markedly risen since vaccine production ceased in 1999. METHODS: From 1996 to 2013, the Naval Health Research Center conducted FRI surveillance at 8 military recruit training centers in the United States. During this period, 58 103 FRI pharyngeal swab specimens were studied, yielding 37 048 adenovirus-positive cases, among which 64% were typed. RESULTS: During the 2 years after reintroduction of the vaccines, military trainees experienced a 100-fold decline in adenovirus disease burden (from 5.8 to 0.02 cases per 1000 person-weeks, P < .0001), without evidence that vaccine pressure had increased the impact of adenovirus types other than Ad4 and Ad7. Although the percentage of type 14 increased following reintroduction of the vaccination, the actual number of cases decreased. We estimate that the vaccines prevent approximately 1 death, 1100-2700 hospitalizations, and 13 000 febrile adenovirus cases each year among the trainees. CONCLUSIONS: These data strongly support the continued production and use of Ad4 and Ad7 vaccines in controlling FRI among US military trainees. Continued surveillance for emerging adenovirus subtypes is warranted.

Targeting the genital tract mucosa with a lipopeptide/recombinant adenovirus prime/boost vaccine induces potent and long-lasting CD8+ T cell immunity against herpes: importance of MyD88.

Targeting of the mucosal immune system of the genital tract with subunit vaccines has failed to induce potent and durable local CD8(+) T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), which causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8(+) T cell immunity to protect the female genital tract from herpes. The lipopeptide vaccine and the rAdv5 vaccine express the immunodominant HSV-2 CD8(+) T cell epitope (gB(498-505)), and both were delivered intravaginally in the progesterone-induced B6 mouse model of genital herpes. Compared with mice immunized with the homologous lipopeptide/lipopeptide (Lipo/Lipo) vaccine, the Lipo/rAdv5 prime/boost immunized mice 1) developed potent and sustained HSV-specific CD8(+) T cells, detected in both the genital tract draining nodes and in the vaginal mucosa; 2) had significantly lower virus titers; 3) had decreased overt signs of genital herpes disease; and 4) did not succumb to lethal infection (p < 0.005) after intravaginal HSV-2 challenge. Polyfunctional CD8(+) T cells, producing IFN-γ, TNF-α, and IL-2 and exhibiting cytotoxic activity, were associated with protection (p < 0.005). The protective CD8(+) T cell response was significantly compromised in the absence of the adapter MyD88 (p = 0.0001). Taken together, these findings indicate that targeting of the vaginal mucosa with a Lipo/rAdv5 prime/boost vaccine elicits a potent, MyD88-dependent, and long-lasting mucosal CD8(+) T cell protective immunity against sexually transmitted herpes infection and disease.

Development of a novel adenovirus serotype 35 vector vaccine possessing an RGD peptide in the fiber knob and the E4 orf 4, 6, and 6/7 regions of adenovirus serotype 5.

Adenovirus (Ad) vectors based on human adenovirus serotype 5 (Ad5) have attracted significant attention as vaccine vectors for infectious diseases. However, the effectiveness of Ad5 vectors as vaccines is often inhibited by the anti-Ad5 neutralizing antibodies retained by many adults. To overcome this drawback, we focused on human adenovirus serotype 35 (Ad35) vectors with low seroprevalence in adults. Although Ad35 vectors can circumvent anti-Ad5 neutralizing antibodies, vector yields of Ad35 vectors are often inferior to those of Ad5 vectors. In this study, we developed novel Ad35 vectors containing the Ad5 E4 orf 4, 6, and 6/7 or the Ad5 E4 orf 6 and 6/7 for efficient vector production, and compared their properties. These E4-modified Ad35 vectors efficiently propagated to a similar extent at virus titers comparable to those of Ad5 vectors. An Ad35 vector containing the Ad5 E4 orf 4, 6, and 6/7 mediated more efficient transduction than that containing the Ad5 E4 orf 6 and 6/7 in human cultured cells. Furthermore, insertion of an arginine-glycine-aspartate (RGD) peptide in the fiber region of an Ad35 vector containing the Ad5 E4 orf 4, 6, and 6/7 significantly improved the transgene product-specific antibody production following intramuscular administration in mice. The Ad35 vector containing the RGD peptide mediated efficient vaccine effects even in the mice pre-immunized with an Ad5.

Comparative immunogenicity of monovalent and bivalent adenovirus vaccines carrying spikes of early and late SARS-CoV-2 variants.

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2- to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

Age differentially impacts adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19.

Adenoviral and mRNA vaccines encoding the viral spike (S) protein have been deployed globally to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older individuals are particularly vulnerable to severe infection, probably reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It is nonetheless unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated S protein-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of previous infection with SARS-CoV-2. We found that aging profoundly compromised S protein-specific IgG titers and further limited S protein-specific CD4+ and CD8+ T cell immunity as a probable function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2. Our results demonstrate that primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273 promotes sustained immunological memory in older adults and potentially confers optimal protection against coronavirus disease 2019.

Vaccines for the common cold.

BACKGROUND: The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat and fever (usually < 37.8˚C). The widespread morbidity it causes worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. OBJECTIVES: To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS: We searched CENTRAL (2012, Issue 12), MEDLINE (1948 to January week 1, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013) and LILACS (1982 to January 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of any virus vaccines to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated methodological quality and extracted trial data. Disagreements were resolved by discussion or by consulting a third review author. MAIN RESULTS: This review included one RCT with 2307 healthy participants; all of them were analysed. This trial compared the effect of an adenovirus vaccine against a placebo. No statistically significant difference in common cold incidence was found: there were 13 events in 1139 participants in the vaccines group and 14 events in 1168 participants in the placebo group; risk ratio (RR) 0.95, 95% confidence interval (CI) 0.45 to 2.02, P = 0.90). No adverse events related to the live vaccine were reported. AUTHORS' CONCLUSIONS: This Cochrane review has found a lack of evidence on the effects of vaccines for the common cold in healthy people. Only one RCT was found and this did not show differences between comparison groups; it also had a high risk of bias. There are no conclusive data to support the use of vaccines for preventing the common cold in healthy people. We identified the need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Unless RCTs provide evidence of a treatment effect and the trade-off between potential benefits and harms is established, policy-makers, clinicians and academics should not recommend the use of vaccines for preventing the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety and mortality related to the vaccine.

Type-I IFN signaling is required for the induction of antigen-specific CD8(+) T cell responses by adenovirus vector vaccine in the gut-mucosa.

Adenovirus vector (Adv) vaccination at a systemic site, such as intramuscular (i.m.) immunization, can induce antigen-specific CD8(+) T cell responses in both systemic and mucosal compartments. It remains unclear, however, how antigen-specific CD8(+) T cell response is induced in the mucosa. In this study, we found that type-I IFN signaling is required for the induction of mRNA expression of retinal dehydrogenase in the draining lymph nodes following the i.m. Adv vaccination. We show that type-I IFN signaling is required for the induction of antigen-specific CD8(+) T cell response in the gut-mucosal compartment following the i.m. Adv vaccination.

Historical Investigation of Fowl Adenovirus Outbreaks in South Korea from 2007 to 2021: A Comprehensive Review.

Fowl adenoviruses (FAdVs) have long been recognized as critical viral pathogens within the poultry industry, associated with severe economic implications worldwide. This specific group of viruses is responsible for a broad spectrum of diseases in birds, and an increasing occurrence of outbreaks was observed in the last ten years. Since their first discovery forty years ago in South Korea, twelve antigenically distinct serotypes of fowl adenoviruses have been described. This comprehensive review covers the history of fowl adenovirus outbreaks in South Korea and updates the current epidemiological landscape of serotype diversity and replacement as well as challenges in developing effective broadly protective vaccines. In addition, transitions in the prevalence of dominant fowl adenovirus serotypes from 2007 to 2021, alongside the history of intervention strategies, are brought into focus. Finally, future aspects are also discussed.

A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.

BACKGROUND: A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection. METHODOLOGY: This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method. RESULTS: In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection. CONCLUSIONS: This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.

Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates.

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.

Single-Dose Immunization With a Chimpanzee Adenovirus-Based Vaccine Induces Sustained and Protective Immunity Against SARS-CoV-2 Infection.

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Comparison of immunity against canine distemper, adenovirus and parvovirus after vaccination with two multivalent canine vaccines.

BACKGROUND: Viral diseases are a major cause of morbidity and mortality in puppies. There is a belief among veterinary practitioners and even educational institutions that the vaccines made in Brazil against canine distemper virus (CDV), canine parvovirus (CPV) and canine adenovirus (CAV) are ineffective or only partially effective. OBJECTIVES: This study aimed at comparing the immunity of two multivalent vaccines in adult dogs in the city of Uberlândia, Minas Gerais state, Brazil. METHODS: The study was carried out at the Animal Protection Association and a total of 60 adult mongrel dogs were selected and divided into two groups. Group A was immunized with two doses of Elevencell® vaccine and Group B received two doses of imported vaccine from the United States; each group was made up of 14 females and 14 males. RESULTS: In group A, the Elevencell vaccine generated a protective antibody titre against CDV in 26 out of 28 subjects (92.85%), CPV in 24 out of 28 subjects (85.71%) and CAV in 26 out of 28 subjects (92.85%). In group B, the imported US vaccine generated a protective antibody titre against CDV in 22 out of 28 subjects (78.57), CPV in 21 out of 28 subjects (75%) and CAV in 25 out of 28 subjects (89.28%). There was no statistical difference between titres generated between vaccine types for any of the three diseases tested. CONCLUSION: Elevencell vaccine titres were not inferior to the imported US vaccine in conferring protective titres against CDV, CPV and CAH, which confirms the efficacy of this product.

1IFN-α Modulates Memory Tfh Cells and Memory B Cells in Mice, Following Recombinant FMDV Adenoviral Challenge.

Follicular helper T (Tfh) cells regulate high-affinity antibody production. Some findings have indicated that Tfh cells could be differentiated into memory cells. Here we have investigated the effects of IFN-α, as an adjuvant, on the generation of memory Tfh cell and memory B cell responses. The data showed that adenoviral vectors expressing: (i) foot-and-mouth disease virus (FMDV) VP1 proteins and porcine IFN-α, or (ii) porcine IFN-α alone, potently enhanced the generation of memory Tfh cells, especially the CCR7 lo memory Tfh subset. Upon rechallenge with FMD recombinant adenoviral vaccines, IFN-α enhances Tfh cells activity, rapidly upregulating their signature Bcl-6, CXCR5, and IL-21 markers. The results suggest that IFN-α enhances the levels of the transcription factor Bcl-6 within Tfh cells, potentially by regulating STAT1. Additionally, IFN-α substantially increased the number of IgG1+ and CD86+ memory B cells, which are responsible for inducing the rapid effector functions of memory Tfh cells after vaccine reactivation, establishing the close relationship between memory B cell and memory Tfh cell subsets. In brief, IFN-α enhances the potency of FMD recombinant adenoviral vaccines to induce memory Tfh and memory B cell responses, thus elevating serum antibody titers. IFN-α administration therefore represents an attractive strategy for enhancing responses to vaccination.

Enhanced protective immune response to PCV2 adenovirus vaccine by fusion expression of Cap protein with InvC in pigs.

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 post-immunization (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.

Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases.

In some serotypes of adenovirus (Ad), the penton base and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can be internalized and used to deliver the vaccine antigens and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important pathogen, causing seriously economic loss to poultry industry in China and other counties. Pt-Dd particles from FAdV-4 infected cells, as well as in those infected with recombinant human Ad expressing fiber-1, fiber-2, and penton base of FAdV-4, were visualized by transmission electron microscopy. For the first time, we proved that FAdV-4 produced Pt-Dd in infected cells. Pt-Dd can also be assembled by the overexpressed recombinant proteins fiber-1, fiber-2, and penton base. Pt-Dd, as well as the recombinant proteins fiber-1, fiber-2, and penton base, were then used to immunize chickens. The humoral immune response, expression of selected immune molecules and challenge results were used to evaluate the immune efficacy of the vaccine candidates. Pt-Dd induced the highest level of enzyme-linked immunosorbent assay antibodies and significant high levels (p < 0.05) of interferonγ, interleukin-4, and major histocompatibility complex II expression in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, and fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton base (67%). The present study showed that FAdV-4 -Pt-Dd and recombinant fiber-1 are promising FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.