Whole-virus Vaccine Research Articles

Antibody Responses in Cats Following Primary and Annual Vaccination against Feline Immunodeficiency Virus (FIV) with an Inactivated Whole-Virus Vaccine (Fel-O-Vax® FIV).

Although the antibody response induced by primary vaccination with Fel-O-Vax® FIV (three doses, 2–4 weeks apart) is well described, the antibody response induced by annual vaccination with Fel-O-Vax® FIV (single dose every 12 months after primary vaccination) and how it compares to the primary antibody response has not been studied. Residual blood samples from a primary FIV vaccination study (n = 11), and blood samples from cats given an annual FIV vaccination (n = 10), were utilized. Samples from all 21 cats were tested with a commercially available PCR assay (FIV RealPCRTM), an anti-p24 microsphere immunoassay (MIA), an anti-FIV transmembrane (TM; gp40) peptide ELISA, and a range of commercially available point-of-care (PoC) FIV antibody kits. PCR testing confirmed all 21 cats to be FIV-uninfected for the duration of this study. Results from MIA and ELISA testing showed that both vaccination regimes induced significant antibody responses against p24 and gp40, and both anti-p24 and anti-gp40 antibodies were variably present 12 months after FIV vaccination. The magnitude of the antibody response against both p24 and gp40 was significantly higher in the primary FIV vaccination group than in the annual FIV vaccination group. The differences in prime versus recall post-vaccinal antibody levels correlated with FIV PoC kit performance. Two FIV PoC kits that detect antibodies against gp40, namely Witness® and Anigen Rapid®, showed 100% specificity in cats recently administered an annual FIV vaccination, demonstrating that they can be used to accurately distinguish vaccination and infection in annually vaccinated cats. A third FIV PoC kit, SNAP® Combo, had 0% specificity in annually FIV-vaccinated cats, and should not be used in any cat with a possible history of FIV vaccination. This study outlines the antibody response to inactivated Fel-O-Vax® FIV whole-virus vaccine, and demonstrates how best to diagnose FIV infection in jurisdictions where FIV vaccination is practiced.

The 2020 race towards SARS-CoV-2 specific vaccines.

The global outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a requirement for two pronged clinical interventions such as development of effective vaccines and acute therapeutic options for medium-to-severe stages of “coronavirus disease 2019" (COVID-19). Effective vaccines, if successfully developed, have been emphasized to become the most effective strategy in the global fight against the COVID-19 pandemic. Basic research advances in biotechnology and genetic engineering have already provided excellent progress and groundbreaking new discoveries in the field of the coronavirus biology and its epidemiology. In particular, for the vaccine development the advances in characterization of a capsid structure and identification of its antigens that can become targets for new vaccines. The development of the experimental vaccines requires a plethora of molecular techniques as well as strict compliance with safety procedures. The research and clinical data integrity, cross-validation of the results, and appropriated studies from the perspective of efficacy and potently side effects have recently become a hotly discussed topic.In this review, we present an update on latest advances and progress in an ongoing race to develop 52 different vaccines against SARS-CoV-2. Our analysis is focused on registered clinical trials (current as of November 04, 2020) that fulfill the international safety and efficacy criteria in the vaccine development. The requirements as well as benefits and risks of diverse types of SARS-CoV-2 vaccines are discussed including those containing whole-virus and live-attenuated vaccines, subunit vaccines, mRNA vaccines, DNA vaccines, live vector vaccines, and also plant-based vaccine formulation containing coronavirus-like particle (VLP). The challenges associated with the vaccine development as well as its distribution, safety and long-term effectiveness have also been highlighted and discussed.

Increasing Efficacy of Enveloped Whole-Virus Vaccines by In situ Immune-Complexing with the Natural Anti-Gal Antibody.

The appearance of variants of mutated virus in course of the Covid-19 pandemic raises concerns regarding the risk of possible formation of variants that can evade the protective immune response elicited by the single antigen S-protein gene-based vaccines. This risk may be avoided by inclusion of several antigens in vaccines, so that a variant that evades the immune response to the S-protein of SARS-CoV-2 virus will be destroyed by the protective immune response against other viral antigens. A simple way for preparing multi-antigenic enveloped-virus vaccines is using the inactivated whole-virus as vaccine. However, immunogenicity of such vaccines may be suboptimal because of poor uptake of the vaccine by antigen-presenting-cells (APC) due to electrostatic repulsion by the negative charges of sialic-acid on both the glycan-shield of the vaccinating virus and on the carbohydrate-chains (glycans) of APC. In addition, glycan-shield can mask many antigenic peptides. These effects of the glycan-shield can be reduced and immunogenicity of the vaccinating virus markedly increased by glycoengineering viral glycans for replacing sialic-acid units on glycans with α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). Vaccination of humans with inactivated whole-virus presenting α-gal epitopes (virusα-gal) results in formation of immune-complexes with the abundant natural anti-Gal antibody that binds to viral α-gal epitopes at the vaccination site. These immune-complexes are targeted to APC for rigorous uptake due to binding of the Fc portion of immunecomplexed anti-Gal to Fcγ receptors on APC. The APC further transport the large amounts of internalized vaccinating virus to regional lymph nodes, process and present the virus antigenic peptides for the activation of many clones of virus specific helper and cytotoxic T-cells. This elicits a protective cellular and humoral immune response against multiple viral antigens and an effective immunological memory. The immune response to virusα-gal vaccine was studied in mice producing anti-Gal and immunized with inactivated influenza-virusα-gal. These mice demonstrated 100-fold increase in titer of the antibodies produced, a marked increase in T-cell response, and a near complete protection against challenge with a lethal dose of live influenza-virus, in comparison to a similar vaccine lacking α-gal epitopes. This glycoengineering can be achieved in vitro by enzymatic reaction with neuraminidase removing sialic-acid and with recombinant α1,3galactosyltransferase (α1,3GT) synthesizing α-gal epitopes, by engineering host-cells to contain several copies of the α1,3GT gene (GGTA1), or by transduction of this gene in a replication-defective adenovirus vector into host-cells. Theoretically, these methods for increased immunogenicity may be applicable to all enveloped viruses with N-glycans on their envelope.

Research Progress on a SARS-CoV-2 Vaccine in China

Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations.

Effect of Virus-Inactivating Agents on the Immunogenicity of Hantavirus Vaccines against Hemorrhagic Fever with Renal Syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by the orthohantaviruses Puumala, Dobrava-Belgrad (four genotypes), Hantaan (genotype Amur), and Seoul. In the Russian Federation, HFRS occupies the leading place among all natural focal human diseases. Formaldehyde, β-propiolactone, and ultraviolet radiation were tested to select the optimal method for viral inactivation during the development of a whole-virion vaccine against HFRS. The specific activity and the immunogenicity of the vaccine were determined, respectively, by the number of copies of viral RNA per 1 mL and by the neutralizing antibodies in the blood sera of BALB/c mice in response to immunization. Analysis of the immunogenicity of vaccines inactivated with formaldehyde, β-propiolactone, or UV radiation did not find significant differences in the level of induced neutralizing antibodies. At the same time, β-propiolactone has obvious technological advantages as compared to formaldehyde and UV radiation: the time of viral inactivation is reduced by dozens of times; neutralization of the inactivator and control of its content in the final vaccine are not required; and the amount of inappropriate protein in the vaccine is decreased due to the decrease in protein aggregation.

Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses.

Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety.

Safety and immunogenicity of an alum-adjuvanted whole-virion H7N9 influenza vaccine: a randomized, blinded, clinical trial

ObjectivesA case of H7N9 influenza virus infection was first identified in China in 2013. This virus is considered to have high pandemic potential. Here we developed an H7N9 influenza vaccine containing an aluminium adjuvant and evaluated the safety and immunogenicity of the vaccine. MethodsFrom October 2017 through August 2018 we conducted a randomized, double-blinded, single-centre phase I clinical trial in China among 360 participants aged ≥12 years. All participants received two doses of the vaccine (7.5, 15 or 30 μg haemagglutinin antigen) or placebo at an interval of 21 days. Adverse event data were collected for 30 days after vaccination. Serum samples were collected on days 0, 21 and 42 for the haemagglutinin inhibition (HI) antibody assay. ResultsA total of 347 participants (347/360, 96.4%) completed the study. The proportions of vaccine-related adverse events after one injection were 56.7% (34/60) in the 7.5-μg group, 86.7% (52/60) in the 15-μg group and 86.7% (52/60) in the 30-μg group. The proportions of adverse events after two injections were less than those reported after the first dose. None of the serious adverse events were related to the vaccine. After receiving two doses of the 7.5-μg vaccine, the proportion of participants achieving an HI titre of ≥40 was 98.2% (55/56, 95%CI 72.3~100.0%), with a geometric mean titre (GMT) of 192.6 (95%CI 162.9~227.8). ConclusionsThe alum-adjuvanted H7N9 whole-virion inactivated vaccine was safe and strongly immunogenic in a population aged ≥12 years.

Schmallenberg Virus: To Vaccinate, or Not to Vaccinate?

Schmallenberg virus (SBV), a teratogenic orthobunyavirus that infects predominantly ruminants, emerged in 2011 in Central Europe, spread rapidly throughout the continent, and subsequently established an endemic status with re-circulations to a larger extent every 2 to 3 years. Hence, it represents a constant threat to the continent’s ruminant population when no effective countermeasures are implemented. Here, we discuss potential preventive measures to protect from Schmallenberg disease. Previous experiences with other arboviruses like bluetongue virus have already demonstrated that vaccination of livestock against a vector-transmitted disease can play a major role in reducing or even stopping virus circulation. For SBV, specific inactivated whole-virus vaccines have been developed and marketing authorizations were granted for such preparations. In addition, candidate marker vaccines either as live attenuated, DNA-mediated, subunit or live-vectored preparations have been developed, but none of these DIVA-capable candidate vaccines are currently commercially available. At the moment, the licensed inactivated vaccines are used only to a very limited extent. The high seroprevalence rates induced in years of virus re-occurrence to a larger extent, the wave-like and sometimes hard to predict circulation pattern of SBV, and the expenditures of time and costs for the vaccinations presumably impact on the willingness to vaccinate. However, one should bear in mind that the consequence of seronegative young animals and regular renewed virus circulation might be again more cases of fetal malformation caused by an infection of naïve dams during one of their first gestations. Therefore, an appropriate and cost-effective strategy might be to vaccinate naïve female animals of all affected species before the reproductive age.

Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models.

Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1-/- mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers.

Immune Response and Protective Efficacy of Inactivated and Live Influenza Vaccines Against Homologous and Heterosubtypic Challenge.

Inactivated (whole-virion, split, subunit, and adjuvanted) vaccines and live attenuated vaccine were tested in parallel to compare their immunogenicity and protective efficacy. Homologous and heterosubtypic protection against the challenge with influenza H5N1 and H1N1 viruses in a mouse model were studied. Single immunization with live or inactivated whole-virion H5N1 vaccine elicited a high level of serum antibodies and provided complete protection against the challenge with the lethal A/Chicken/Kurgan/3/05 (H5N1) virus, whereas application of a single dose of the split vaccine was much less effective. Adjuvants increased the antibody levels. Addition of the Iso-SANP adjuvant to the split vaccine led to a paradoxical outcome: it increased the antibody levels but reduced the protective effect of the vaccine. All tested adjuvants shifted the ratio between IgG1 and IgG2a antibodies. Immunization with any of the tested heterosubtypic live viruses provided partial protection against the H5N1 challenge and significantly reduced mouse mortality, while inactivated H1N1 vaccine offered no protection at all. More severe course of illness and earlier death were observed in mice after immunization with adjuvanted subunit vaccines followed by the challenge with the heterosubtypic virus compared to challenged unvaccinated animals.

Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies.

Novel Coronavirus COVID-19: Current Evidence and Evolving Strategies.

FeLV-infection: problems and prospects of vaccine prevention and interferon-therapy of feline leukemia

Here, we review an overall effectiveness of interferon-based preparations and interferon biosynthesis inducers for treatment of feline leukemia, as well as development of methodological approaches to improve efficacy of interferon therapy. Feline leukemia is a systemic hematopoietic malignancy caused by a single-stranded RNA retrovirus called Feline Leukemia Virus (FeLV) that leads to lethal outcome within about 3 years after the onset. FelV is widely distributed in population of domestic cats worldwide, being often detected in the blood of wild cats, including those of rare and endangered species. In some regions, FeLV prevalence may be high not only among domestic cats, but among wild as well. Currently, there are several commercially available vaccines to protect cats from FeLV infection (e.g., inactivated whole-virion vaccines such as Nobivac adjuvanted Feline 2-FeLV, two-adjuvant subunit vaccine FeLV-derived protein antigens as well as non-adjuvanted vector DNA vaccine). However, none of such vaccines provides durable protection. In addition, vaccination of cats against FeLV is often associated with development of diverse inflammatory, allergic and shock complications, and highly serious side effects such as developing vaccine-associated sarcoma at the injection site that some researchers connect with use of adjuvants like aluminum salts etc. We briefly describe FeLV virus, pathogenetic parametersassociated with FeLV infection as well as current technologies for preventing and treating feline leukemia. A historic background and current state of interferon therapy for FeLV infection as well as associated neoplastic processes in domestic cats and some wild species are evaluated. Possible interventions aimed at improving efficiency of interferon therapy of feline leukemia based on using new recombinant interferon preparations of various types and subtypes, as well as interferon inducers are discussed. In conclusion, it is noted that another interesting and potentially highly promising option in defining strategy of biotherapy associated with modulating IFN system in FeLV-infected animals might be to use of synthetic inducers triggering endogenous IFN production.

Foot-and-Mouth Disease Virus Lacking the Leader Protein and Containing Two Negative DIVA Markers (FMDV LL3B3D A24) Is Highly Attenuated in Pigs.

Inactivated whole-virus vaccines are widely used for the control of foot-and-mouth disease (FMD). Their production requires the growth of large quantities of virulent FMD virus in biocontainment facilities, which is expensive and carries the risk of an inadvertent release of virus. Attenuated recombinant viruses lacking the leader protease coding region have been proposed as a safer alternative for the production of inactivated FMD vaccines (Uddowla et al., 2012, J Virol 86:11675-85). In addition to the leader deletion, the marker vaccine virus FMDV LL3BPVKV3DYR A24 encodes amino acid substitutions in the viral proteins 3B and 3D that allow the differentiation of infected from vaccinated animals and has been previously shown to be effective in cattle and pigs. In the present study, two groups of six pigs each were inoculated with live FMDV LL3BPVKV3DYR A24 virus either intradermally into the heel bulb (IDHB) or by intra-oropharyngeal (IOP) deposition. The animals were observed for 3 or 5 days after inoculation, respectively. Serum, oral and nasal swabs were collected daily and a thorough postmortem examination with tissue collection was performed at the end of the experiment. None of the animals had any signs of disease or virus shedding. Virus was reisolated from only one serum sample (IDHB group, sample taken on day 1) and one piece of heel bulb skin from the inoculation site of another animal (IDHB group, necropsy on day 3), confirming that FMDV LL3BPVKV3DYR A24 is highly attenuated in pigs.

Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and may Elicit NS1-Specific Antibody Responses in Vaccinated Individuals.

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, namely FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific Western blot analysis also detected anti-NS1 antibodies in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

Limited protection against γ-herpesvirus infection by replication-deficient virus particles.

The γ-herpesviruses have proved hard to vaccination against, with no convincing protection against long-term latent infection by recombinant viral subunits. In experimental settings, whole-virus vaccines have proved more effective, even when the vaccine virus itself establishes latent infection poorly. The main alternative is replication-deficient virus particles. Here high-dose, replication-deficient murid herpesvirus-4 only protected mice partially against wild-type infection. By contrast, latency-deficient but replication-competent vaccine protected mice strongly, even when delivered non-invasively to the olfactory epithelium. Thus, this approach seems to provide the best chance of a safe and effective γ-herpesvirus vaccine.

Влияние инактивирующих вирус агентов на иммуногенность вакцин против геморрагической лихорадки с почечным синдромом

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by orthohantavirases Puumala, Dobrava-Belgrad (4 genotypes), Hantaan (genotype Amur) and Seoul.. In the Russian Federation, HFRS takes a leading place among all natural focal human diseases. Formalin, β-propiolactone, and ultraviolet radiation were tested to select the optimal method of virus inactivation during the development of the whole-virion vaccine against HFRS. The specific activity and the immunogenicity of the vaccine were determined, respectively, by the number of copies of viral RNA/mL and by the titer of neutralizing antibodies in the BALB/c mice blood serum in response to immunization. An analysis of the immunogenicity of vaccines inactivated with formalin, β-propiolactone or UV radiation did not reveal significant differences in the level of neutralizing antibodies they induced. At the same time, β-propiolactone has obvious technological advantages compared to formalin and UV radiation: the time of inactivation of hantavirus is reduced tenfold, neutralization of the inactivator and control of its content in the final vaccine are not required, and the amount of total protein in the vaccine decreases. hemorrhagic fever with renal syndrome, hantavirases, inactivated vaccines, neutralizing antibodies, formalin, β-propiolactone, ultraviolet

The stability and immunogenicity of inactivated MDCK cell-derived influenza H7N9 viruses

In recent years, cell-based influenza vaccines have gained a great interest over the egg-based vaccines. Several inactivated H7N9 vaccines have been evaluated in clinical trials, including whole-virion vaccines, split vaccines and subunit vaccines. Recently, we developed a new suspension MDCK (sMDCK) cell line for influenza viruses production. However, the properties of purified antigen from sMDCK cells remain unclear. In this study, the stability of influenza H7N9 vaccine bulk derived from sMDCK cells was investigated, and the data were compared with the vaccine antigen derived from our characterized adhesion MDCK (aMDCK) cells in serum-free medium. The influenza H7N9 bulks derived from sMDCK and aMDCK cells were stored at 2–8 °C for different periods of time, and a number of parameters selected to monitor the H7N9 vaccine antigen stability were evaluated at each interval (1, 3 and 12 months). The monitored parameters included virus morphology, hemagglutinin (HA) activity, HA concentration, antigenicity, and immunogenicity. The sMDCK-derived H7N9 bulk showed similar morphology to that of the aMDCK-derived H7N9 bulk, and there were no obvious changes after the extended storage periods. Furthermore, the HA titer, HA concentration, and antigenicity of sMDCK-derived H7N9 bulk were stable after 28 months of storage. Finally, the results of hemagglutination inhibition and neutralization tests showed that sMDCK- and aMDCK-derived H7N9 vaccines had comparable immunogenicity. These results indicated that sMDCK-derived H7N9 bulk has good stability compared to that of aMDCK-derived H7N9 bulk. Thus, the newly developed suspension MDCK cell line shows a great alternative for manufacturing cell-based influenza vaccines.

Recombinant baculovirus vaccine expressing hemagglutinin of H7N9 avian influenza virus confers full protection against lethal highly pathogenic H7N9 virus infection in chickens.

The emergent highly pathogenic avian influenza A (H7N9) (HPAI) virus is a major public concern in China. Therefore, it is crucially important to develop an effective vaccine against this virus. In this study, we constructed a baculovirus vaccine expressing the hemagglutinin (HA) of H7N9 strain A/Chicken/Jiaxing/148/2014 (JX148). The recombinant baculovirus (rBac-JX148HA) generated in this study showed good growth in insect cells and good safety, and it stably expressed the HA protein. We compared the immunogenicity and efficacy of the inactivated whole-virus vaccine JX148 and rBac-JX148HA. One chicken in the JX148-treated group died on day 4 post-challenge, and three chickens had typical clinical symptoms (survival rate, 90%; morbidity, 40%). However, no chickens immunized with rBac-JX148HA showed clinical signs during the 14-day observation period. An analysis of viral shedding and viral replication demonstrated that rBac-JX148HA more efficiently inhibited viral shedding and viral replication than the inactivated whole-virus vaccine. Taken together, these results indicate that the inactivated recombinant baculovirus vaccine induces a high hemagglutination inhibition antibody titer, provides complete protection against challenge with the highly pathogenic H7N9 virus, and effectively inhibits viral shedding. Therefore, the candidate vaccine has potential utility in the prevention and control of H7N9 avian influenza and is also appropriate for veterinary vaccines using cell suspension culture technology.

A pilot comparative study of recombinant protein and whole-virus inactivated vaccines against porcine circovirus type 2 in conventionally reared pigs

Porcine circovirus type 2 (PCV2) causes porcine circovirus-associated disease, which is characterized by systemic wasting syndrome, including respiratory problems worldwide. Most commercial PCV2 vaccines are derived from recombinant capsid protein or inactivated whole-virus. We compared average daily weight gain, interferon-γ, and neutralizing antibody levels of a recombinant protein vaccine and an inactivated whole-virus vaccine in a pilot study. Both PCV2 vaccines showed similar effect on immunity against PCV2 and a better average daily weight gain was found in both vaccinated groups compared to non-vaccinated animals.

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

ABSTRACT Coxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality.