Inactivated Virus Vaccine Research Articles

Humoral and cellular immune response to AZD1222 /Covishield and BV152/Covaxin COVID-19 vaccines among adults in India

ABSTRACT Several COVID-19 vaccines were developed using different approaches to prevent both symptomatic COVID-19 cases and fatalities. The adults were vaccinated with two doses of AZD1222/Covishield (n = 77) [manufactured by Serum Institute of India Pvt Ltd] vaccine and BV152/Covaxin (n = 99) [manufactured by Bharat Biotech] vaccine. They were assessed for immune response at pre-vaccination, 1 month post first and 6 months post second dose for anti-SARS-CoV-2 IgG antibody, surrogate neutralizing antibody (NAbs), immune phenotypes, antigen specific NK, B and T cell response, their effector functionality by ELISPOT and plasma cytokine profile. Both vaccines elicited enhanced IgG antibody and Nab levels compared to the baseline. BV152/Covaxin, the whole virus inactivated vaccine exhibited higher IgG (70% vs 100%), Nab (90% vs 100%), and robust T cell (31% vs 96%) responses at 6 months post second dose compared to 1 month post first dose justifying the utility of the second dose. Detection of SARS-CoV-2 WV and S1 specific CD4+ central T cell memory response in AZD1222/Covishield vaccinee at 6 months post second dose and higher CD4+ and CD8+ naïve and central memory T cell response in BV152/Covaxin vaccinee at 1 month post first dose indicated the involvement of memory T cells. Persistent IgG and NAb responses along with IgG+B and IgG+memory B cells in AZD1222/Covishield recipients at 6 months post second dose indicated sustained immune memory response. Continued heightened IFN-γ secreting T cell response (ELISPOT) displayed by both the vaccine platforms could serve as a co correlate of protection, further to evaluation in follow up studies. Overall, our data suggest that coordinated functions of humoral and cellular branches of adaptive immunity may pave ways toward protective immunity against COVID-19.

Recombinant avian-derived antiviral proteins cIFITM1, cIFITM3, and cViperin as effective adjuvants in inactivated H9N2 subtype avian influenza vaccines

Vaccine adjuvants, serving as non-specific immune enhancers, play a pivotal role in the immunoprevention and control of animal diseases. This study utilized prokaryotic expression systems to express and purify chicken-derived cIFITM1, cIFITM3, and cViperin, which were then formulated as adjuvants with H9N2 avian influenza virus antigens to create inactivated vaccines. These vaccines were administered to SPF chickens to investigate their immunopotentiating functions. Additionally, the proteins were assessed for their ability to act as standalone immune enhancers. The results demonstrated that cIFITM1, cIFITM3, and cViperin significantly elevated serum hemagglutination inhibition (HI) antibody titers. Notably, when used individually, these proteins markedly enhanced the antiviral capabilities of challenged chickens, leading to alleviated clinical symptoms, reduced tracheal virus replication, diminished virus shedding, and lessened histopathological damage, with cIFITM1 exhibiting the most pronounced effect. Furthermore, the protective efficacy of two H9N2 recombinant virus inactivated vaccines supplemented with cIFITM1 adjuvant was validated, achieving a 100 % vaccine protection efficiency. In conclusion, cIFITM1, cIFITM3, and cViperin as adjuvants for influenza vaccines effectively inhibit virus replication and shedding, highlighting their significant potential in influenza prevention and control.

MRNA-based influenza vaccine expands breadth of B cell response in humans.

Eliciting broad and durable antibody responses against rapidly evolving pathogens like influenza viruses remains a formidable challenge. The germinal center (GC) reaction enables the immune system to generate broad, high-affinity, and durable antibody responses to vaccination. mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines induce persistent GC B cell responses in humans. Whether an mRNA-based influenza vaccine could induce a superior GC response in humans compared to the conventional inactivated influenza virus vaccine remains unclear. We assessed B cell responses in peripheral blood and draining lymph nodes in cohorts receiving the inactivated or mRNA-based quadrivalent seasonal influenza vaccine. Participants receiving the mRNA-based vaccine produced more robust plasmablast responses and higher antibody titers to H1N1 and H3N2 influenza A viruses and comparable antibody titers against influenza B virus strains. Importantly, mRNA-based vaccination stimulated robust recall B cell responses characterized by sustained GC reactions that lasted at least 26 weeks post-vaccination in three of six participants analyzed. In addition to promoting the maturation of responding B cell clones, these sustained GC reactions resulted in enhanced engagement of low-frequency pre-existing memory B cells, expanding the landscape of vaccine-elicited B cell clones. This translated to expansion of the serological repertoire and increased breadth of serum antibody responses. These findings reveal an important role for the induction of persistent GC responses to influenza vaccination in humans to broaden the repertoire of vaccine-induced antibodies.

Efficacy Evaluation of COVID-19 Vaccines in Patients with Autoimmune Rheumatic Diseases in Mashhad, Iran

vaccination. However, since the majority of studies in the related literature are focused on the efficacy of messenger RNA in rheumatic patients, the present study aimed to assess the efficiency of the inactivated whole virus vaccines and viral vector COVID-19 vaccines in rheumatic diseases in Mashhad, Iran. Methods: This prospective cross-sectional study was conducted on ARDs patients who were referred to private clinics and rheumatologic clinics of Ghaem and Imam Reza Hospitals, Mashhad, Iran, during 2021-22. Anti-neutralizing antibodies have been considered to check antibodies of Sinopharm and Barkat vaccines, and an anti-spike antibody was considered to check Sputnik V and AstraZeneca vaccine antibodies. Humoral immunity was investigated using the anti-spike Enzyme-linked immunosorbent assay and anti-neutralizing antibodies. Results: The obtained results showed that humoral immunity after COVID-19 vaccination was observed in 73.9% of the patients with ARDs. However, humoral immunity was lower in ARDs patients who took tacrolimus and higher in patients with a history of COVID-19 infection (χ2=5.84, p=0.01). The infection after the second COVID-19 vaccination was lower in patients with humoral immunity (χ2=5.69, p=0.01). Conclusion: This study demonstrated that a homologous second dose of an inactivated whole viral vector SARS-CoV-2 vaccine was safe and provided a remarkable antibody response in ARDs patients.

Analysis of the immunological response elicited by a polyvalent foot and mouth disease vaccine and its compatibility with a diva test in Jimma Town, Ethiopia

The research was conducted in Jimma town, Oromiya Regional State, from October 2022 to June 2023, with the aim of assessing the immune response of polyvalent FMD (Foot and Mouth Disease) vaccine. The study involved 34 cattle in a longitudinal study, divided into two groups: 29 vaccinated and 5 unvaccinated. The vaccinated cattle received an inactivated polyvalent FMD virus vaccine produced by the National Veterinary Institute. Blood samples were collected on days 0, 14, 21, 35, 80, and 125 after vaccination and tested using Virus Neutralization Test and 3ABC ELISA. The results showed a significant increase in neutralizing antibodies against structural proteins in all vaccinated cattle on day 14 after vaccination for all three serotypes. (A/ETH/21/2000, p = 0.015; O/ETH/38/2005, p = 0.017; SAT2/ETH/64/2009, p = 0.007). On day, fourteen of post-vaccination vaccinated group showed immune response equal or above 1.5 log10 in a proportion of 69%, 73% and 94% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The status of raised antibody titer on day 125 post-vaccination showed decreasing by 14%, 18% and 4% for serotype A/ETH/21/2000, O/ETH/38/2005 and SAT2/ETH/64/2009 respectively. The DIVA test, or 3ABC ELISA, used to differentiate infected from vaccinated animals, revealed the absence of immune response to the Non-structural protein in the vaccinated cattle group. Conversely, the unvaccinated group showed no recorded antibody titer to both structural and non-structural proteins. In summary, the commercially available FMD vaccine, comprising serotype A, O, and SAT2, triggers an immune response to the structural protein rather than the non-structural protein after the initial administration. This outcome implies that FMD vaccines from the National Veterinary Institute align with the DIVA test. Nevertheless, additional efforts may be necessary to bolster the strength and duration of the vaccine-induced immune response.

Molecular genetic methods for quality control of inactivated vaccines using a Chikungunya virus model: vaccine strain identification and completeness of virus inactivation

INTRODUCTION. The completeness of virus inactivation and the identity of the vaccine strain are essential parameters for the safety and quality of inactivated virus vaccines, which should be controlled during vaccine development and production. Currently, the most promising quality control methods for inactivated virus vaccines are molecular genetic methods, which provide rapid results with high sensitivity and specificity.AIM. The aim of this study was the development of a real-time quantitative polymerase chain reaction (qPCR) method and an integrated cell culture real-time quantitative polymerase chain reaction (ICC-qPCR) method to assess the completeness of virus inactivation, as well as a reverse-transcription polymerase chain reaction assay coupled with restriction fragment length polymorphism analysis (RT-PCR-RFLP) to confirm the identity of the vaccine virus strain.MATERIALS AND METHODS. This study used RNA of CHIKV genotypes (three strains of each of the four CHIKV genotypes, including Asian, West African (WAf), and East/Central/South African (ECSA) genotypes, and the Indian Ocean Lineage of the ECSA genotype (ECSA-IOL), which were identified by sequencing prior to analysis). Additionally, the study used the Nika21 CHIKV strain (ECSA genotype), the Nika21 CHIKV strain inactivated with β-propiolactone, and the Nika21 CHIKV strain antigen adsorbed on aluminium hydroxide. The methods used included real-time qPCR, RT-PCR-RFLP, and virus neutralisation.RESULTS. The study identified a 218 bp fragment of the nsP1 gene (positions 789 to 1006) with restriction endonuclease recognition sites. These sites were present or absent in combinations specific to each of the four CHIKV genotypes. The authors selected primers for amplification of the specified gene region and tested the conditions for real-time qPCR and RT-PCR-RFLP. The study demonstrated the possibility of using the ICC-qPCR method to confirm the completeness of virus inactivation and the RT-PCR-RFLP method to identify the vaccine strain.CONCLUSIONS. The study showed the advantages of using the ICC-qPCR method to confirm the completeness of antigen inactivation and the RT-PCR-RFLP method to identify the vaccine strain. These methods are more sensitive and faster than traditional culture methods. ICC-qPCR and RT-PCR-RFLP can be used at any stage of the production process for inactivated vaccines.

Determination of T cell response against XBB variants in adults who received either monovalent wild type inactivated whole virus or mRNA vaccine or bivalent WT/BA.4-5 COVID-19 mRNA vaccine as the additional booster

ObjectivesAs the SARS-CoV-2 virus evolves more rapidly than vaccines are updated, T cell immunity potentially confers protection against disease progression and death from new variants. In this study, we aimed to assess whether the current boosting vaccination schemes offer sufficient T cell protection against new SARS-CoV-2 variants. Methods. 292 adults who had received the second booster of either monovalent wild type vaccines (inactivated virus or mRNA) (cohort 1) or the second/third booster of bivalent WT/BA.4-5 mRNA vaccine (cohort 2) were recruited in Hong Kong. All participants showed no serological evidence of recent infection of SARS-CoV-2. Blood samples of each participant were collected before and one-month after receiving the booster. T cell and antibody responses were determined by flow cytometry and neutralization test respectively. Results. Among all vaccination strategies, only the adults who had received the bivalent vaccine as the third booster dose significantly elicited T cell responses to the XBB variant. Either monovalent or bivalent mRNA but not inactivated virus vaccine as the second/third booster induced antibody against different XBB variants. Conclusions. Receiving bivalent mRNA vaccine as the third booster is preferrable to induce both T cell and antibody responses against XBB.

The effectiveness of COVID-19 vaccination in preventing hospitalisation and mortality: A nationwide cross-sectional study in Iran.

The pandemic of the coronavirus disease 2019 (COVID-19) led to a global health crisis, prompting widespread vaccination efforts to reduce severe outcomes. In this study, we assessed the impact of mass COVID-19 vaccination on hospitalisation and mortality rates in Iran, where over 83% of the vaccinated population received inactivated virus vaccines. Using retrospective, cross-sectional analysis, we examined data from the Iran Health Insurance Organisation, covering 41 million individuals from 20 February 2020 to 20 March 2022. We analysed hospital records from 956 Iranian hospitals, focusing on inpatient stays, short-term hospitalisations, and emergency department visits. Study outcomes included COVID-19 hospital admissions and associated mortality. We used negative binomial regression to compare hospital admission rates between periods, while we used a poison regression model with a log link to assess mortality risks before and after vaccination. Among 806 076 hospital admissions, 57 599 deaths were recorded. COVID-19 hospitalisations increased with age, and women had slightly higher admission rates than men. Advanced age and male sex correlated with higher mortality rates. Hospital admissions rose to 1178.66 per million population per month post-vaccination compared to 459.78 pre-vaccination. The incidence rate ratio was 2.09 (95% confidence interval (CI) = 1.90-2.32, P < 0.001), mainly due to the Delta variant. In contrast, post-vaccination mortality rates decreased from 111.33 to 51.66 per 1000 admissions per month. Post-vaccination, COVID-19 mortality significantly decreased, with a relative risk being 0.61 (95% CI = 0.60-0.62, P < 0.001) across all age groups and sexes. The Delta variant increased hospital admissions among vaccinated individuals, but widespread vaccination significantly reduced COVID-19-related mortality.

Comparison of post-COVID-19 pulmonary complications in individuals vaccinated with BioNTech or Sinovac

Aims: Although several research have been undertaken to investigate the impact of the vaccination on long Coronavirus Disease 2019 (COVID-19) syndrome or post-acute sequelae, there is a lack of published evidence on the long-term effects of vaccines on lung-sequelae-related disease. Considering the limited global COVID-19 vaccine distribution, it is essential to establish the impact of vaccination in reducing pulmonary complications. Turkey has been offering COVID-19 vaccines from two platforms, including BNT162b2 (Pfizer-BioNTech, mRNA vaccine) and CoronaVac (Sinovac, inactivated vaccine). This study aimed to evaluate the efficacy of BioNTech and Sinovac vaccines in reducing post-COVID-19 pulmonary complications in individuals. Methods: A total of 94 patients COVID-19 pneumonia patients who were categorized based on the quantity of BioNTech or Sinovac vaccines they received before their first COVID-19 infection were included. The inclusion criteria consisted of a confirmed diagnosis of COVID-19 pneumonia through polymerase chain reaction testing, availability of the mentioned before and follow-up computed tomography scans, and administration of at least one dose of vaccine. Results: The number of complications in patients fully vaccinated with Sinovac and who experienced post-COVID lung complications was significantly greater than in those vaccinated with BioNTech. The C-reactive protein and D-Dimer measurements of individuals who experienced complications in the Sinovac vaccinated group were significantly elevated on the index date. Conclusion: The quantity of lung sequelae after COVID and laboratory parameters indicating this result were found to be higher in inactivated virus vaccines than in mRNA vaccines. This suggests that the protection of inactivated vaccines may be insufficient in severe cases.

Adjuvant Use of the Invariant-Natural-Killer-T-Cell Agonist α-Galactosylceramide Leads to Vaccine-Associated Enhanced Respiratory Disease in Influenza-Vaccinated Pigs.

Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), provide a universal source of T-cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines. An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD). This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which purportedly causes enhanced virus fusion activity to the host cell and increased infection. Here, we show that αGC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2 Abs, αGC elicits high concentrations of interferon (IFN)-γ-secreting cells both in the lungs and systemically. Additionally, we found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection compared to an OIW adjuvant. Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity.

Inactivated LMBV vaccine with nano‑aluminum adjuvant provided immune protection in largemouth bass (Micropterus Salmoides)

Largemouth bass ranavirus (LMBV) has caused severe economic losses in largemouth bass (Micropterus salmoides) aquaculture. Vaccination is acknowledged as an efficient strategy to prevent viral diseases in fish. In this study, an inactivated virus vaccine with nano‑aluminum adjuvant was successfully developed to protect largemouth bass effectively against LMBV. LMBV was inactivated by formalin and mixed with nano‑aluminum adjuvant under moderate agitation. The nano‑aluminum hydroxide adjuvant showed a cuboidal structure under the scanning transmission electron microscope (STEM), scanning electron microscope (SEM), and transmission electron microscope (TEM), and LMBV antigen-adsorbing rate was 39.49 % superior to those of micro‑aluminum hydroxide and IMS1312 adjuvants. The results from both external and internal damage assessments indicated that the nano‑aluminum vaccine had good safety for Micropterus salmoides. The relative percentage of survival was 80 % with a booster immunization in largemouth bass. The expression levels of immune-related genes such as TNF-α, IFN, and IL-8 were significantly up-regulated in the spleen of fish immunized by nano‑aluminum adjuvant vaccine compared to those in inactivated LMBV and control groups. The neutralizing antibody in nano‑aluminum adjuvant vaccine group showed higher abundance and lasted for a longer period. Lymphocytes from the head kidney of largemouth bass in the nano‑aluminum adjuvant vaccine group showed stronger proliferation activity in vitro post-stimulation with ConA. Moreover, stronger migration of the dendritic cells was induced by the nano‑aluminum adjuvant vaccine. Collectively, our findings suggested that the inactivated LMBV vaccine with nano‑aluminum adjuvant could provide efficient protection for largemouth bass against LMBV infection. The nano‑aluminum adjuvant has potential application with inactivated viral vaccines in fish.

An effective vaccine against influenza A virus based on the matrix protein 2 (M2)

The ever-increasing antigenic diversity of the hemagglutinin (HA) of influenza A virus (IAV) poses a significant challenge for effective vaccine development. Notably, the matrix protein 2 (M2) is a highly conserved 97 amino acid long transmembrane tetrameric protein present in the envelope of IAV. More than 99 % of IAV strains circulating in American swine herds share the identical pandemic (pdm) isoform of M2, making it an ideal target antigen for a vaccine that could elicit broadly protective immunity. Here, using soluble nanoscale membrane assemblies termed nanodiscs (NDs), we designed this membrane mimetic nanostructures displaying full-length M2 in its natural transmembrane configuration (M2ND). Intramuscular (IM) immunization of swine with M2ND mixed with conventional emulsion adjuvant elicited M2-specific IgG antibodies in the serum that recognized influenza virions and M2-specific interferon-γ secreting cells present in the blood. Intranasal (IN) immunization with M2ND adjuvanted with a mycobacterial extract elicited M2-specific IgA in mucosal secretions that also recognized IAV. Immunization with an influenza whole inactivated virus (WIV) vaccine supplemented with a concurrent IM injection of M2ND mixed with an emulsion adjuvant increased the level of protective immunity afforded by the former against a challenge with an antigenically distinct H3N2 IAV, as exhibited by an enhanced elimination of virus from the lung. The lone IM administration of the M2ND vaccine mixed with an emulsion adjuvant provided measurable protection as evidenced by a >10-fold reduction or complete elimination of the challenge virus from the lung, but it did not diminish the viral load in nasal secretions nor the extent of pneumonia that ensued after the virus challenge. In contrast, an improved formulation of the M2ND vaccine that incorporated synthetic CpG oligodeoxynucleotides (CpG-ODN) in the nanostructures administered alone, via the IN and IM routes combined, provided a significant level of protective immunity against IAV as evidenced by a decreased viral load in both the upper and lower respiratory tracts and fully eliminated the occurrence of pneumonia in 89 % of the pigs immunized with this biologic. Notably, to be effective, the M2 protein must be displayed in the ND assemblies, as shown by the observation that simply mixing M2 with empty NDs incorporating CpG-ODN (eND-CpG-ODN) did not provide protective immunity. This novel M2-based vaccine offers great promise to help increase the breadth of protection afforded by conventional WIV vaccines against the diversity of IAV in circulation and, plausibly, as a broadly protective stand-alone biologic.

CoronaVac-vaccinated kidney transplant recipients with hybrid immunity have strong neutralizing responses against Omicron and Mu variants of SARS-CoV-2.

Neutralizing antibody (nAb) responses against SARS-CoV-2 variants after inactivated virus vaccine (CoronaVac) in kidney transplant recipients (KTRs) with or without SARS-CoV-2 infection history remains unclear. We aimed to evaluate the neutralizing antibody responses against emerging SARS-CoV-2 variants after two doses of CoronaVac in these patients. 22.2% of participants had hybrid immunity. Anti-spike IgG antibodies were evidenced in 44% of the patients. nAbs against B.1.111, Mu, and Omicron were detected in 28.5%, 17.9%, and 21.4% of naïve KTRs, respectively. Furthermore, nearly 100% of KTRs with hybrid immunity had nAbs against the variants evaluated. Thus, a significant proportion of infection-naïve KTRs had no detectable nAb titers against Mu and Omicron variants after two doses of the CoronaVac vaccine. However, the nAb titers were significantly higher in patients with hybrid immunity, and it was no association between the immunosuppressive regimen and the seropositivity rate of anti-SARS-CoV-2 neutralizing antibodies. Therefore, hybrid KTRs are protected against COVID-19 by emerging variants able to escape from vaccine-elicited nAbs such as Mu and Omicron.

Comparison of antigen-specific B cell responses reveals disparity in immunogenicity and memory B cell formation across COVID-19 vaccine platforms

Various vaccine technologies have been employed in the coronavirus disease 2019 (COVID-19) vaccines, including whole inactivated virus (WIV), recombinant protein, mRNA, and nanoparticle vaccines. To elucidate the cellular mechanisms underlying the immune responses elicited by different vaccines, we examined and compared antigen-specific B cell responses targeting the receptor-binding domain (RBD) of the viral spike protein. We found that the nanoparticle vaccine pathogen-like antigens-RBD (PLA-RBD) and the mRNA vaccine demonstrated superior immunogenicity compared with the WIV vaccine and the RBD-dimer, a recombinant protein vaccine. Interestingly, the WIV vaccine contains toll-like receptor ligands that enhance IgG2a/c class-switching. For the mRNA vaccine, although it induces robust germinal center responses and T follicular helper (Tfh) cells, it has limited ability to induce memory B cells and long-lived plasma cells. These results indicate that vaccine formats significantly influence both the quantity and quality of immune responses, providing valuable insights for the future development of vaccines.

Virus-like Particles for Disease Diagnosis and Drug Delivery Applications

Abstract: Virus-like particles (VLPs) are nanoscale, self-assembling cage structures made out of proteins with practical uses in biomedicine. They might be used to create better vaccinations, imaging equipment, gene and drug therapy delivery systems, and in vitro diagnostic equipment. VLPs are nanostructures that might be used in medicine, immunization, and diagnostics, among other areas. Many VLPs-based vaccines are now in use for the treatment of infectious diseases, and many more are on their way to clinical testing thanks to recent advancements in biomedical engineering. Although VLPs exhibit promising qualities in terms of efficacy, safety, and diversity, they may become more widely used in the future. Vaccines based on virus-like particles (VLPs) might serve as an effective addition to current immunization strategies for the prevention and treatment of emerging infectious diseases. The growing field of healthcare prevention has become increasingly interested in VLPs, leading to the discovery of various VLP-based candidate vaccines for vaccination towards a wide range of infectious pathogens, one of the most recent that has been developed is the vaccine against SARS-CoV-2, the effectiveness of that is now being tested. VLPs can elicit both antibody and cell-mediated immune responses, unlike standard inactivated viral vaccines. However, several problems persist with this surface display method and will need fixing in the future. VLPs-based medicinal delivery, nanoreactors for treatment, and imaging systems are being developed with promising results. The latest developments in the generation and fabrication of VLPs involve explorations of several expression systems for their creation and their application as vaccines for the avoidance of infectious diseases and malignancies. This manuscript offers the most advanced perspective on biomedical applications based on VLPs, as well as details innovative methods for manufacturing, functionalization, and delivery of VLPs.

Influence of commercial inactivated or modified-live virus vaccination at time of AI on corpus luteum development and function in beef cattle

Our objective was to evaluate the effect of vaccination with an inactivated virus vaccine (IVV) or modified-live virus (MLV) vaccine on the corpus luteum (CL). On d0, synchronized beef cows were treated with MLV (n = 70; BoviShield Gold FP5VL5), IVV (n = 16; ViraShield 6VL5HB), or were unvaccinated controls (n = 5). Plasma was collected from treated animals on d0 and every other day through d22. Plasma was analyzed for concentrations of progesterone and 15 cytokines. Between d10 and d13, selected females (n = 13) were ovariectomized; controls were slaughtered on d15/16 to obtain CL for histological evaluation. There were reduced numbers of large luteal cells (LLC) in MLV compared to IVV and controls (P < 0.0001), but IVV were similar to controls (P = 0.11). MLV had decreased LLC percentage compared to controls, and IVV were intermediate (P < 0.0001, MLV: 1.57 ± 0.33 %, IVV: 2.99 ± 0.30 %, Control: 6.45 ± 0.33 %). Based on progesterone concentrations, 24 % MLV and 0 % IVV had an abnormal cycle following vaccination. Overall, MLV had reduced progesterone concentrations (P = 0.02; MLV: 3.61 ± 0.22; IVV: 4.81 ± 0.46 ng/mL). The new CL that formed following an abnormal cycle in MLV had the greatest percentage (35.56 ± 5.5 %) of apoptotic cells. Treatment by cycle status interaction, and time significantly affected IFN-γ, IP-10, MIP-1β, and MCP-1 (P < 0.03), with several time points having elevated concentrations in abnormally cycling MLV animals. Collectively, this demonstrates MLV vaccination around estrus negatively influenced LLC, progesterone, and increased luteal apoptosis and pro-inflammatory cytokines.

Production and evaluation of three kinds of vaccines against largemouth bass virus, and DNA vaccines show great application prospects

Largemouth bass virus (LMBV) infections has resulted in high mortality and economic losses to the global largemouth bass industry and has seriously restricted the healthy development of the bass aquaculture industry. There are currently no antiviral therapies available for the control of this disease. In this study, we developed three types of vaccine against LMBV; whole virus inactivated vaccine (I), a subunit vaccine composed of the major viral capsid protein MCP (S) as well as an MCP DNA vaccine(D), These were employed using differing immunization and booster strategies spaced 2 weeks apart as follows: II, SS, DD and DS. We found that all vaccine groups induced humoral and cellular immune responses and protected largemouth bass from a lethal LMBV challenge to varying degrees and DD produced the best overall effect. Specifically, the levels of specific IgM in serum in all immunized groups were elevated and significantly higher than those in the control group. Moreover, the expression of humoral immunity (CD4 and IgM) and cellular immunity (MHCI-α) as well as cytokines (IL-1β) was increased, and the activity of immunity-related enzymes ACP, AKP, LZM, and T-SOD in the serum was significantly enhanced. In addition, the relative percent survival of fish following an LMBV lethal challenge 4 weeks after the initial immunizations were high for each group: DD(89.5 %),DS(63.2 %),SS(50 %) and II (44.7 %). These results indicated that the MCP DNA vaccine is the most suitable and promising vaccine candidate for the effective control of LMBV disease.

Evaluation of protective immune response of immersion inactivated vaccine against Singapore grouper iridovirus

Singapore grouper iridovirus (SGIV) always causes high transmission efficiency and mortality in the larval and juvenile stages of grouper in aquaculture industry. Although inactivated virus and recombinant DNA vaccines administered via intraperitoneal injection have shown efficacy in protection against SGIV, their potential applications in field testing were limited due to the vaccine delivery methods. Here, we developed an immersion vaccine containing inactivated virus and Montanide IMS 1312 adjuvant (IMS 1312) and evaluated its protective efficacy against SGIV infection. Compared to the PBS group, fish vaccinated with immersion inactivated vaccine with or without IMS 1312 were significantly protected against SGIV, with a relative percent survival (RPS) of 57.69 % and 38.47 %, respectively. Furthermore, the transcripts of viral core genes were reduced, and the histopathological severity caused by SGIV were relatively mild in multiple tissues of the IMS + V group. The immersion vaccine activated the AKP and ACP activities and increased the mRNA levels of IFN and inflammation-associated genes. The transcriptome analysis showed that a total of 731 and 492 genes were significantly regulated in the spleen and kidney from the IMS + V group compared to the PBS group, respectively. Among them, 129 DEGs were co-regulated, and enriched in the KEGG pathways related to immune and cell proliferation, including MAPK signaling, JAK-STAT signaling and PI3K-Akt signaling pathways. Similarly, the DEGs specially regulated in the kidney and spleen upon vaccine immunization were significantly enriched in the KEGG pathways related to interferon and inflammation response. Together, our results elucidated that the immersion vaccine of inactivated SGIV with IMS 1312 induced a protective immune response of grouper against SGIV.

The Impact of COVID-19 Vaccination Side-Effects on Work Attendance among Saudi Healthcare Workers.

This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. The majority of participants were female (83.7%) and aged 25-34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic.

Orally dissolving film as a potential vaccine delivery carrier to prevent influenza virus infection

Orally dissolving films (ODF) are designed to be dissolved on the tongue and absorbed in the mouth. It offers multiple advantages over the commonly used needle-based vaccines, especially in terms of convenience allowing safe, painless, and easy self-administration. As the efficacy of ODF-encapsulated influenza vaccines has not been demonstrated, we assessed the protection elicited by inactivated influenza virus (A/PR/8/34, H1N1) vaccine delivered using ODFs in mice. Trehalose and pullulan components of the ODF ensured that the HA antigens of the inactivated PR8 virus retained their stability while ensuring the rapid release of the vaccines upon exposure to murine saliva. Mice were immunized thrice by placing the PR8-ODF on the tongues of mice at 4-week intervals, and vaccine-induced protection was evaluated upon lethal homologous challenge infection. The PR8-ODF vaccination elicited virus-specific serum IgG and IgA antibody responses, hemagglutinin inhibition (HAI), and viral neutralization. Upon challenge infection, ODF vaccination showed higher levels of IgG and IgA antibody responses in the lungs and antibody-secreting cell (ASC) responses in both lung and spleen compared to unimmunized controls. These results corresponded with the enhanced T cell and germinal center B cell responses in the lungs and spleens. Importantly, ODF vaccination significantly reduced lung virus titers and inflammatory cytokines (IFN-γ, IL-6) production compared to unvaccinated control. ODF vaccination ensured 100% survival and prevented weight loss in mice. These findings suggest that influenza vaccine delivery through ODFs could be a promising approach for oral vaccine development.