Trivalent Inactivated Vaccine Research Articles

Comparison of immunogenicity of adjuvanted and high dose influenza vaccination in long-term care facility residents.

The CDC recommends the more immunogenic adjuvanted and high-dose flu vaccines over standard-dose, non-adjuvanted vaccines for individuals above 65 years old. The current study compares adjuvanted trivalent inactivated flu vaccine (aTIV, FLUAD) versus high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met non-inferiority standards for older long-term care facility (LTCF) residents. We collected blood from long-term care facility residents participating in a randomized 1:1 active control trial comparing MF59C.1 adjuvanted trivalent inactivated flu vaccine, aTIV versus HD-IIV3 over the course of two flu seasons, 2018-2019 and 2019-2020 (Trial, NCT03694808). We assessed humoral immunity at set time points via hemagglutinin inhibition assays (HAI) and anti-neuraminidase (enzyme-linked lectin assays (ELLA)). The recombinant influenza vaccine (RIV, Flublok) was assessed similarly in year two for a small number of participants who were carried over from year 1 (n=32). We enrolled 387 volunteers and administered either aTIV (n=194), HD-IIV3 (n=193) over the course of the 2018-2019 and 2019-2020 flu seasons. Among those enrolled and randomized in year one, a subset were administered RIV and studied in year two (n = 32). At 28 days post-vaccination, aTIV exhibited non-inferiority to HD-IIV3 for HAI for both H1N1 and H3N2 strains (GMT ratios (95% CI) for HD-IIV3/aTIV of 1.03(0.76, 1.4) and 1.04(0.73, 1.48), respectively; both 95% CI upper bounds < 1.5 to meet non-inferiority criteria) but not for Influenza B (GMT ratio (95% CI) = 1.21 (0.91, 1.61)). Non-inferiority criteria for HAI seroconversion were not met for any of the three strains. Applying the same non-inferiority criteria to neuraminidase inhibition (NI), both day 28 titer and seroconversion in aTIV were non-inferior to HD-IIV3 for H1N1 and H3N2 strains. Both aTIV and HD-IIV3 elicited similar immune responses with robust antibody responses. For the primary outcome, aTIV is non-inferior to HD-IIV3 for HAI titer of H1N1 and H3N2 but failed to meet non-inferiority criteria for Influenza B and seroconversion for all assessed strains. For the secondary outcome, aTIV was non-inferior to HD-IIV3 for both titer and seroconversion of anti-neuraminidase for both H1N1 and H3N2.

Results of a clinical study of the influenza tetravalent inactivated subunit adjuvant vaccine Grippol Quadrivalent in children aged 6 months to 5 years (inclusive)

The article presents the results of a clinical investigation on the administration of the Grippol Quadrivalent vaccine (influenza tetravalent inactivated subunit adjuvant vaccine) in children from 6 months to 5 years old. The vaccine has demonstrated no less effectiveness in comparison with the Grippol plus vaccine (influenza trivalent inactivated polymer-subunit vaccine).comparable results were obtained for all evaluated indicators of immunological efficacy against matching strains of the influenza virus, while for additional strain B (Yamagata line) there was a statistically significant difference in the increase in the immune response in the Grippol Quadrivalent group. The results of the assessment of the reactogenicity and frequency of systemic adverse events indicated a favorable and comparable safety profile of the vaccines Grippol Quadrivalent and Grippol plus in children from 6 months to 5 years old. The data obtained allowed us to conclude that the immunological efficacy of the Grippol Quadrivalent vaccine is no less when compared to the Grippol plus vaccine, as well as a comparable safety and reactogenicity profile. According to the results of the clinical investigation, on 08/04/2023, the Ministry of Health of the Russian Federation amended the “Instructions for the medical use of the drug”: Grippol Quadrivalent is indicated for children from the age of 6 months.

Immunogenicity, Effectiveness, and Safety of Trivalent Inactivated Influenza Split Vaccine in Patients with Inflammatory Joint Diseases Receiving Modern Antirheumatic Therapy

Immunogenicity, Effectiveness, and Safety of Trivalent Inactivated Influenza Split Vaccine in Patients with Inflammatory Joint Diseases Receiving Modern Antirheumatic Therapy

The Milk of Cows Immunized with Trivalent Inactivated Vaccines Provides Broad-Spectrum Passive Protection against Hand, Foot, and Mouth Disease in Neonatal Mice.

Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A10 (CA10), and Coxsackievirus A6 (CA6). The high pathogenicity of HFMD has garnered significant attention. Currently, there is no specific treatment or broad-spectrum preventive measure available for HFMD, and existing monovalent vaccines have limited impact on the overall incidence or prevalence of the disease. Consequently, with the emergence of new viral strains driven by vaccine pressure, there is an urgent need to develop strategies for the rapid response and control of new outbreaks. In this study, we demonstrated the broad protective effect of maternal antibodies against three types of HFMD by immunizing mother mice with a trivalent inactivated vaccine targeting EV71, CA16, and CA10, using a neonatal mouse challenge model. Based on the feasibility of maternal antibodies as a form of passive immunization to prevent HFMD, we prepared a multivalent antiviral milk by immunizing dairy cows with the trivalent inactivated vaccine to target multiple HFMD viruses. In the neonatal mouse challenge model, this immunized milk exhibited extensive passive protection against oral infections caused by the three HFMD viruses. Compared to vaccines, this strategy may offer a rapid and broadly applicable approach to providing passive immunity for the prevention of HFMD, particularly in response to the swift emergence and spread of new variants.

Hemagglutinin stalk-specific Fc-mediated functions are associated with protection against influenza-illness after seasonal influenza vaccination in pregnant women.

Several influenza vaccine candidates aim to elicit antibodies against the conserved hemagglutinin stalk domain. Understanding the protective mechanism of these antibodies, which mediate broad neutralization and Fc-mediated functions, following seasonal vaccination is critical. Plasma samples were obtained from a subset of pregnant women living with or without HIV-1 enrolled in a randomised trial (138 trivalent inactivated vaccine [TIV] and 145 placebo recipients). Twenty-three influenza-illness cases were confirmed within 6 months postpartum. We measured H1 stalk-specific antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD) and cellular cytotoxicity (ADCC) at enrolment and 1-month post-vaccination. The association between these Fc-mediated functions and protection against influenza-illness following vaccination was examined using multiple logistic regression analysis and risk reduction thresholds were defined by the score associated with the lowest odds of influenza-illness. Amongst TIV and placebo recipients, lower H1 stalk-specific ADCP and ADCD activity was detected for participants with confirmed influenza compared with individuals without confirmed influenza-illness 1-month post-vaccination. Pre-existing ADCP scores ≥250 reduced the odds of A/H1N1 infection (odds ratio 0.11; p=0.01) with an 83% likelihood of risk reduction. Following TIV, ADCD scores of ≥25 and ≥15 significantly reduced the odds against A/H1N1 (0.10; p=0.01) and non-group 1 (0.06; p=0.0004) influenza virus infections, respectively. These ADCD scores were associated with >84% likelihood of risk reduction. H1 stalk-specific ADCC potential was not associated with protection against influenza-illness. H1 stalk-specific ADCD correlates with protection against influenza-illness following influenza vaccination during pregnancy. These findings provide insight into the protective mechanisms of HA stalk antibodies.

Detection of antibodies against structural proteins of foot-and-mouth disease virus in bovines of western Uttar Pradesh, India.

Foot-and-mouth disease (FMD) is considered as one of the most important contagious viral diseases affecting cloven-footed animals. For effective control of FMD, immunization along with herd immunity is essential in the field conditions. To assure and track the coverage and effectiveness of the vaccination program, the serological studies are very much required after the vaccination program. The present study was aimed to investigate the prevalence of antibodies against structural proteins of FMD virus (FMDV) serotypes of O, A and Asia-1 in seven districts of western Uttar Pradesh, India, and assure the efficacy of vaccination under National Animal Disease Control Program. A total of 308 sera samples were collected from apparent healthy vaccinated cattle and buffaloes from seven districts including Amroha, Baghpat, Bareilly, Bulandsahar, Gautam Budh Nagar, Meerut and Muzaffarnagar of western Uttar Pradesh, India. Determination of antibodies against structural proteins of FMDV was carried out using solid-phase blocking enzyme-linked immunosorbent assay. The protective level of the FMDV serotypes O, A and Asia-1 included in the inactivated trivalent vaccine was 66.55, 48.05 and 47.08% in bovines, respectively. To provide the higher level of protection against the circulating FMDV, the present study recommended the thorough investigation of the immunogenic interaction between the vaccine strains and the field strains. Further investigations should also be conducted with larger sample size and across diverse geographical regions to gain a more comprehensive understanding of herd immunity.

Study of antigenic and immunogenic activity of experimental series of inactivated emulsified vaccine against Chicken hemophilosis in laboratory conditions

Worldwide, Avibacterium paragallinarum is the etiological agent of infectious rhinitis in poultry. Most vaccines are based on international reference strains without taking into account the current epizootic situation of hemophilosis in the respective territories. Using a mixture of inactivated Av. paragallinarum antigens (SS 6/20, A; SS 7/20, B; SS 8/20, C) of three serotypes (1:1:1) and (sample No 1 – AG + «aluminum hydroxide»; No 2 – AG + «aluminum hydroxide + saponin»; No 3 – AG + «Montanide ISA 70») obtained experimental samples of the domestic inactivated vaccine against chicken rhinitis. The antigenic and immunogenic activity of the inactivated trivalent vaccine on chickens was established. A commercial vaccine registered on the territory of Ukraine was used as a comparison. Vaccination of birds was carried out twice in a dose of 0.5 cm3 with an interval of 21 days, subcutaneously, in the area of the middle third of the neck. The investigated experimental samples No 2 and No 3 are not inferior to the commercial vaccine in terms of antigenic activity; antibody levels range from 1:64 to 1:512. The immunogenic activity of these samples is 80–100% compared to the commercial vaccine (poultry group 4), the immunogenic activity of which is at the same level. Replication of the causative agent of |Haemophilus infection in chickens from the paternal material of chickens vaccinated with a commercial vaccine (group 4) and experimental vaccines №2 (group 2, adjuvant – «aluminum hydroxide + saponin») and №3 (group 3, adjuvant – «Montanid ISA 70») and infected with control strains of the pathogen was not noted

Influenza Vaccination Implementation in Sri Lanka: A Cost-Effectiveness Analysis.

Influenza causes an estimated 3 to 5 million cases of severe illness annually, along with substantial morbidity and mortality, particularly in low- and middle-income countries (LMICs). Currently, Sri Lanka has no influenza vaccination policies and does not offer vaccination within the public healthcare sector. Therefore, we performed a cost-effectiveness analysis of influenza vaccine implementation for the Sri Lankan population. We designed a static Markov model that followed a population cohort of Sri Lankans in three age groups, 0-4, 5-64, and 65+ years, through two potential scenarios: trivalent inactivated vaccination (TIV) and no TIV across twelve-monthly cycles using a governmental perspective at the national level. We also performed probabilistic and one-way sensitivity analyses to identify influential variables and account for uncertainty. The vaccination model arm reduced influenza outcomes by 20,710 cases, 438 hospitalizations, and 20 deaths compared to no vaccination in one year. Universal vaccination became cost-effective at approximately 98.01% of Sri Lanka's 2022 GDP per capita (incremental cost-effectiveness ratio = 874,890.55 Rs/DALY averted; 3624.84 USD/DALY averted). Results were most sensitive to the vaccine coverage in the 5-64-year-old age group, the cost of the influenza vaccine dose in the 5-64-years-old age group, vaccine effectiveness in the under-5-years-old age group, and the vaccine coverage in the under-5-years-old age group. No value for a variable within our estimated ranges resulted in ICERs above Rs. 1,300,000 (USD 5386.15) per DALY adverted. Providing influenza vaccines was considered highly cost-effective compared to no vaccines. However, large-scale national studies with improved data are needed to better inform estimates and determine the impact of vaccination implementation.

Cost-Effectiveness and Health Impacts of Different Influenza Vaccination Strategies for Children in China

Authors aimed to evaluate the economic and health impacts of three influenza vaccines available in China, including trivalent inactivated vaccine, quadrivalent inactivated vaccine, and live attenuated influenza vaccine, for children aged six months to 18 years. Two decision-analytic models were developed to simulate four vaccination strategies. Outcomes included total costs from a societal perspective in 2021, quality-adjusted life-year loss, numbers of outpatient and inpatient cases, and deaths avoided using each strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the uncertainty of model inputs. For children aged six months to three years, trivalent inactivated vaccine saved $48 million and avoided a loss of 17,637 quality-adjusted life-years compared with no vaccination. For children aged 3-18 years, quadrivalent inactivated vaccine was cost-effective compared with trivalent inactivated vaccine, with an incremental cost-effectiveness ratio of $32,948.5/quality-adjusted life-year (willingness-to-pay threshold=$37,653/quality-adjusted life-year), which was sensitive to the RR of vaccine effectiveness of quadrivalent inactivated vaccine versus of trivalent inactivated vaccine. When compared with quadrivalent inactivated vaccine, live attenuated influenza vaccine was $1.28 billion more costly but gained an additional 13,560 quality-adjusted life-years; its incremental cost-effectiveness ratio was $123,983.8/quality-adjusted life-year. Live attenuated influenza vaccine would be cost-effective if its vaccine effectiveness was >0.79. Probabilistic sensitivity analysis revealed that quadrivalent inactivated vaccine, trivalent inactivated vaccine, live attenuated influenza vaccine, and no vaccination were cost-effective in 55.94%, 33.09%, 10.97%, and 0% of 10,000 Monte Carlo simulations. Trivalent inactivated vaccine was cost-effective compared with no vaccination in children aged six months to 18 years. Of the three vaccination strategies for children aged 3-18 months, quadrivalent inactivated vaccine appears to be the most cost-effective.

Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine.

The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2). We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016. We account for the changes in routine immunization schedules and varying implementation of preventive and outbreak response SIAs, assuming homogenous coverages of 50% and 80% for SIAs. In areas with strong routine immunization, the switch from tOPV to bOPV has likely resulted in gains in population immunity to types 1 and 3 poliovirus. However, we estimate that improved immunogenicity of new schedules has not compensated for declines in preventive SIAs in areas with weak routine immunization. For type 2 poliovirus, without tOPV in routine immunization or SIAs, mucosal immunity has declined nearly everywhere, while use of mOPV2 has created highly heterogeneous population immunity for which it is important to take into account when responding to cVDPV2 outbreaks. The withdrawal of tOPV and declining allocations of resources for preventive bOPV SIAs have resulted in reduced immunity in vulnerable areas to types 1 and 3 poliovirus and generally reduced immunity to type 2 poliovirus in the regions studied, assuming homogeneous coverages of 50% and 80% for SIAs. The very low mucosal immunity to type 2 poliovirus generates substantially greater risk for further spread of cVDPV2 outbreaks. Emerging gaps in immunity to all serotypes will require judicious targeting of limited resources to the most vulnerable populations by the Global Polio Eradication Initiative (GPEI).

Characterization of a highly virulent Avibacterium paragallinarum isolate.

Infectious coryza (IC) is an important respiratory infectious disease in chickens. In this study, an Avibacterium paragallinarum Page serovar C strain, named ZJ-C, was isolated from a local layer flock that was routinely vaccinated with an inactivated trivalent vaccine, using reference strain Modesto as the serovar C immunogen. The pathogenicity, immunogenicity, and genetic characteristics of ZJ-C were studied. The minimum pathogenic dose of the isolate was 100 CFU, which was 1/1,000 of the dose of the serovar C reference strain Modesto. The vaccination-challenge trial in specific pathogen-free (SPF) chickens showed that the ZJ-C bacterin could provide 100% protection against challenge from both ZJ-C and Modesto strains, whereas Modesto provided 100% protection against challenge from itself, but only 70% protection against ZJ-C. Sequence analysis of the HMTp210 hypervariable region (region 2) showed that the homology of region 2 between ZJ-C and Modesto was 96.14%, whereas the homology between ZJ-C and the Kume serovar C-4 reference strain HP60 was 99.83%. Phylogenetic analysis of region 2 showed that ZJ-C was most closely related to cluster C-4, represented by HP60. The experimental data obtained in this study will help the selection of optimal vaccine strains and assist serotyping studies of Av. paragallinarum.

Evaluation of Seasonal Inactivated Influenza Vaccines Prophylactic Efficacy

Relevance. Seasonal flu vaccination is still the most effective way to protect against flu viruses and help to reduce the burden of flu illnesses. Another possible benefit is the impact of yearly vaccines on severity of breakthrough infection. In this regard, the issue of choosing safe vaccine with high immunogenicity becomes relevant.Aims. To evaluate the prophylactic efficacy of inactivated seasonal flu vaccines (quadrivalent subunit vaccine with adjuvant and trivalent vaccine) and reactogenicity of quadrivalent vaccine.Materials and methods. 491 cases were included in our study: 152 cases received adjuvanted quadrivalent subunit flu vaccine «Grippol Quadrivalent», 118 cases received trivalent inactivated flu vaccine and 221 cases who have received no vaccinations during 2018–2019 epidemic season.Results. inactivated vaccines showed high prophylactic efficacy in preventing seasonal influenza. Incidence of influenza and other viral respiratory disease cases was lowest in «Grippol Quadrivalent» group. Breakthrough influenza cases in individuals vaccinated with inactivated vaccine were predominantly mild, no severe cases were reported. The early post-vaccination period in «Grippol Quadrivalent» group showed no variation in adverse events with other vaccines.Conclusion. Adjuvanted quadrivalent subunit flu vaccine was the most efficacious in preventing influenza in 2018–2019 epidemic season.

The Protective Efficacy of an Inactivated Vaccine against Avibacterium paragallinarum Field Isolates.

Simple SummaryThe incidence of infectious coryza has increased in China, even occurring in vaccinated chickens, causing serious economic losses. Several researchers believe that mutation, the increased virulence of Avibacterium paragallinarum, and improper vaccination procedures lead to poor protection from an inactivated vaccine. Based on this, the purpose of the current study was to evaluate the protective efficacy of a commercial infectious coryza trivalent inactivated vaccine against field infection of Avibacterium paragallinarum in China. Our results suggested that double vaccination showed better protection efficacy than single vaccination. The clinical symptoms, pathological changes, and bacterial shedding of chickens with double vaccination were significantly lower than those of control groups after challenge with field Avibacterium paragallinarum isolates of three serovars. No significant differences were found in body weight and egg production between the boost vaccination groups and the negative control group. The current commercial vaccine shows comparable efficacy in shortening the course of infection if administered twice. Our results provide a reference for infectious coryza clinical vaccine application in China. In addition, better ventilation strategies and biosecurity are important components of a strategic plan to prevent infectious coryza.Infectious coryza (IC) is an acute respiratory disease caused by Avibacterium paragallinarum (Av. paragallinarum). In recent years, there have been frequent outbreaks of IC in chickens vaccinated with an inactivated vaccine, causing huge losses to the poultry industry. In this study, the protective efficacy of the trivalent inactivated IC vaccine (PT Medion Farma Jaya) against the field isolates of three serovars of Av. paragallinarum was verified. After vaccination, the hemagglutination inhibition antibody titers in double-vaccinated groups (A2, B2, and C2) were higher than those in single-vaccinated groups (A1, B1, and C1). The highest antibody titer was 213.1 at 3 weeks after the booster vaccination in group A2. Consistent with the trend in hemagglutination inhibition antibody titers, the protective efficacy of double vaccination was better than that of single vaccination. The clinical symptoms and pathological changes were alleviated, or the bacterial shedding was significantly reduced with double vaccination after challenge with field isolates of three serovars (p < 0.05). In particular, the chickens with double vaccination showed no clinical symptoms, pathological changes, or bacterial shedding after challenge by the serovar C strain. There was no significant difference in body weight and egg production between the double-vaccinated groups and the negative control group (p > 0.05). Therefore, we recommend that the commercial IC vaccine should be double-vaccinated in clinical applications.

Cost Effectiveness of Quadrivalent Versus Trivalent Inactivated Influenza Vaccines for the Portuguese Elderly Population.

Background: quadrivalent inactivated vaccine (QIV) has replaced trivalent inactivated vaccine (TIV). In Portugal, TIV is free of charge for risk groups, including older adults (≥65 years old). In its turn, QIV—which provides broader protection as it includes an additional lineage B strain—was introduced in Portugal in October 2018; only since the 2019/20 influenza season has it been provided free of charge for risk groups. This study evaluates the cost effectiveness of switching from TIV to QIV, from the National Health Service perspective, in the Portuguese elderly mainland population. Methods: A decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the incremental cost-effectiveness ratio (ICER). In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results: the high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of EUR 5,283,047, and the resulting ICER would be EUR 26,403,007/QALY, above the usual willingness-to-pay threshold. Conclusions: from the National Health Service perspective, our findings reveal that QIV is not cost effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost effective.

The Efficacy of a Trivalent Inactivated Salmonella Vaccine Combined with the Live S. Gallinarum 9R Vaccine in Young Layers after Experimental Infections with S. Enteritidis, S. Typhimurium, and S. Infantis.

Worldwide, poultry infections by Salmonella are the cause of significant economic losses, not only due to reduced production (due to fowl typhoid disease), but also considering the efforts and control measures that must be constantly applied, especially due to zoonotic serovars. Poultry is a common reservoir of Salmonella and its transmission into the food chain is a risk for humans. The vaccination of layers plays an important role in the overall efforts to prevent Salmonella infections. An inactivated trivalent vaccine was prepared with S. Enteritidis, S. Typhimurium, and S. Infantis strains. Infection trials were performed to evaluate the efficacy of three vaccination schedules using inactivated and live S. Gallinarum 9R vaccines. For this purpose, at week 5 of life, one subcutaneous dose of live S. Gallinarum 9R vaccine (1–5 × 107 CFU) was given to Groups 1 and 2. At weeks 8 and 11 of life, chickens were also vaccinated with one (Group 1) or two (Groups 2 and 3) intramuscular doses of the inactivated oil-adjuvant trivalent vaccine (1 × 108 CFU/dose of each antigen). Group 4 consisted of chickens that remained unvaccinated (control). At week 14 of life, the efficacy of the vaccination plans was evaluated in three separate inoculation trials with S. Enteritidis, S. Typhimurium, or S. Infantis. After vaccination with the inactivated vaccine, homologous antibody production was observed, and after challenge, a significant reduction in the faecal shedding, invasion, and colonization of S. Typhimurium and S. Infantis was achieved by all vaccination schedules, while the vaccination with at least one dose of the live S. Gallinarum 9R vaccine was necessary to obtain such a significant protection against S. Enteritidis infection.

Protective efficacy of an H5/H7 trivalent inactivated vaccine (H5-Re13, H5-Re14, and H7-Re4 strains) in chickens, ducks, and geese against newly detected H5N1, H5N6, H5N8, and H7N9 viruses

Some H5 viruses isolated in poultry or wild birds between 2020 and 2021 were found to be antigenically different from the vaccine strains (H5-Re11 and H5-Re12) used in China. In this study, we generated three new recombinant vaccine seed viruses by using reverse genetics and used them for vaccine production. The vaccine strain H5-Re13 contains the hemagglutinin (HA) and neuraminidase (NA) genes of an H5N6 virus that bears the clade 2.3.4.4h HA gene, H5-Re14 contains the HA and NA genes of an H5N8 virus that bears the clade 2.3.4.4b HA gene, and H7-Re4 contains the HA and NA genes of H7N9 virus detected in 2021. We evaluated the protective efficacy of the novel H5/H7 trivalent inactivated vaccine in chickens, ducks, and geese. The inactivated vaccine was immunogenic and induced substantial antibody responses in the birds tested. Three weeks after vaccination, chickens were challenged with five different viruses detected in 2020 and 2021: three viruses (an H5N1 virus, an H5N6 virus, and an H5N8 virus) bearing the clade 2.3.4.4b HA gene, an H5N6 virus bearing the clade 2.3.4.4h HA gene, and an H7N9 virus. All of the control birds shed high titers of virus and died within 4 days post-challenge, whereas the vaccinated chickens were completely protected from these viruses. Similar protective efficacy against H5 viruses bearing the clade 2.3.4.4h or 2.3.4.4b HA gene was observed in ducks and geese. Our study indicates that the newly updated H5/H7 vaccine can provide solid protection against the H5 and H7N9 viruses that are currently circulating in nature.

Influenza Vaccination Results in Differential Hemagglutinin Stalk-Specific Fc-Mediated Functions in Individuals Living With or Without HIV

Influenza virus hemagglutinin (HA) stalk-specific antibodies have been shown to potently induce Fc-mediated effector functions which are important in protection from disease. In placebo-controlled maternal influenza (MatFlu) vaccination trials of pregnant women living with or without HIV, reduced risk of influenza illness was associated with high HA stalk antibody titers following trivalent inactivated vaccination (TIV). However, the mechanisms of immunity conferred by the HA stalk antibodies were not well understood. Here, we investigated HA stalk-specific Fc effector functions including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and FcγRIIa and FcγRIIIa binding in response to seasonal influenza vaccination. These were measured pre- and 1-month post-vaccination in 141 HIV-uninfected women (67 TIV and 74 placebo recipients) and 119 women living with HIV (WLWH; 66 TIV and 53 placebo recipients). In contrast to HIV-uninfected women, where HA stalk-specific ADCP and FcγRIIa binding were significantly boosted, WLWH showed no increase in response to vaccination. HA stalk-specific ADCC potential and FcγRIIIa binding were not boosted regardless of HIV status but were higher in WLWH compared with HIV-uninfected women prior to vaccination. HA stalk-specific ADCD was significantly increased by vaccination in all women, but was significantly lower in the WLWH both pre- and post- vaccination. Co-ordination between HA stalk-specific ADCP and ADCD in WLWH was improved by vaccination. Fc polyfunctionality was enhanced by vaccination in HIV-uninfected women and driven by the HA stalk antibody titers. However, in the WLWH, higher pre-vaccination Fc polyfunctionality was maintained post-vaccination but was decoupled from titer. Overall, we showed differential regulation of Fc effector HA stalk responses, suggesting that HIV infection results in unique humoral immunity in response to influenza vaccination, with relevance for future strategies that aim to target the HA stalk in this population.

Comparative efficacy and safety of vaccines to prevent seasonal influenza: A systematic review and network meta-analysis

SummaryBackgroundInfluenza is one of the most common respiratory viral infections worldwide. Numerous vaccines are used to prevent influenza. Their selection should be informed by the best available evidence. We aimed to estimate the comparative efficacy and safety of seasonal influenza vaccines in children, adults and the elderly.MethodsWe conducted a systematic review and network meta-analysis (NMA). We searched the Cochrane Library Central Register of Controlled Trials, MEDLINE and EMBASE databases, and websites of regulatory agencies, through December 15th, 2020. We included placebo- or no vaccination-controlled, and head-to-head randomized clinical trials (RCTs). Pairs of reviewers independently screened the studies, abstracted the data, and appraised the risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was laboratory-confirmed influenza. We also synthesized data for hospitalization, mortality, influenza-like illness (ILI), pneumonia or lower respiratory-tract disease, systemic and local adverse events (AEs). We estimated summary risk ratios (RR) using pairwise and NMA with random effects. This study is registered with PROSPERO, number CRD42018091895.FindingsWe identified 13,439 citations. A total of 231 RCTs were included after screening: 11 studies did not provide useful data for the analysis; 220 RCTs [100,677 children (< 18 years) and 329,127 adults (18–60 years) and elderly (≥ 61 years)] were included in the NMA. In adults and the elderly, all vaccines, except the trivalent inactivated intradermal vaccine (3-IIV ID), were more effective than placebo in reducing the risk of laboratory-confirmed influenza, with a RR between 0.33 (95% credible interval [CrI] 0.21–0.55) for trivalent inactivated high-dose (3-IIV HD) and 0.56 (95% CrI 0.41–0.74) for trivalent live-attenuated vaccine (3-LAIV). In adults and the elderly, compared with trivalent inactivated vaccine (3-IIV), no significant differences were found for any, except 3-LAIV, which was less efficacious [RR 1.41 (95% CrI 1.04–1.88)]. In children, compared with placebo, RR ranged between 0.13 (95% CrI 0.03–0.51) for trivalent inactivated vaccine adjuvanted with MF59/AS03 and 0.55 (95% CrI 0.36–0.83) for trivalent inactivated vaccine. Compared with 3-IIV, 3-LAIV and trivalent inactivated adjuvanted with MF59/AS03 were more efficacious [RR 0.52 (95% CrI 0.32–0.82) and RR 0.23 (95% CrI 0.06–0.87)] in reducing laboratory-confirmed influenza. With regard to safety, higher systemic AEs rates after vaccination with 3-IIV, 3-IIV HD, 3-IIV ID, 3-IIV MF59/AS03-adj, quadrivalent inactivated (4-IIV), quadrivalent adjuvanted (4-IIV MF59/AS03-adj), quadrivalent recombinant (4-RIV), 3-LAIV or quadrivalent live attenuated (4-LAIV) vaccines were noted in adults and the elderly [RR 1.5 (95% CrI 1.18–1.89) to 1.15 (95% CrI 1.06–1.23)] compared with placebo. In children, the systemic AEs rate after vaccination was not significantly higher than placebo.InterpretationAll vaccines cumulatively achieved major reductions in the incidence of laboratory-confirmed influenza in children, adults, and the elderly. While the live-attenuated was more efficacious than the inactivated vaccine in children, many vaccine types can be used in adults and the elderly.FundingThe directorate general of welfare, Lombardy region.

Influenza vaccination influencing level of specific humoral immunity in healthy individuals

To assess an effect of vaccination on the level of humoral anti-influenza herd immunity, 2955 sera were collected and analyzed by HIT in the 2019–2020 and 2020–2021 epidemiological seasons. All sera were obtained from healthy adult donors residing in various cities of the Russian Federation. Among them, 1057 volunteers were vaccinated with seasonal influenza trivalent inactivated vaccine. Characteristics of humoral anti-influenza immunity (average geometric antibody titers and the proportion of individuals seropositive for the vaccine viruses) obtained in autumn 2019 and 2020 (1–2 months after vaccination) in vaccinated individuals vs. unvaccinated subjects were found to be markedly higher evidencing about a positive vaccination-related contribution to developing herd immunity against influenza in the preepidemic periods. After the 2019–2020 influenza epidemic, in spring 2020 (6–7 months after vaccination), the levels of antibodies to all vaccine components decreased by 2.6–3.5-fold in vaccinated donors compared to the pre-epidemic period in 2019 autumn. Antibody titers became substantially lower than the protective level (titer by HIT 1/40). At the same time, no significant differences between the groups of vaccinated vs. unvaccinated individuals were observed afterwards. This indicates instability of post-vaccination anti-influenza humoral immunity. As a result, it may decrease an influenza-resistant population cohort of working age on the eve of new epidemic season. The immunogenicity of the inactivated trivalent seasonal influenza vaccine was estimated by HIT while analyzing paired sera obtained from 295 and 112 healthy individuals of various ages vaccinated in autumn 2019 and 2020, respectively. The response to the vaccine was found to be age-related. Children aged 3–14 years vs. older subjects showed a more efficient response. Insufficient immunogenicity of influenza B virus vaccine components was shown. In all age groups, average geometric titers for influenza B virus antibodies were lower (2–8-fold) than for current A(H1N1)pdm09-like strains and influenza A(H3N2) viruses 1–1.5 months post-vaccination. Analyzing vaccine immunogenicity showed a significant inverse relationship between the level of preexisting strain-specific serum antibodies before vaccination and formation of antibodies to the corresponding vaccine virus 1–1.5 months after vaccination. Seroconversion to each vaccine component was remarkably more frequent in individuals with a low preexisting level of antibodies specific to the corresponding virus.

Results of clinical trials of a trivalent vaccine for horses

We have developed a trivalent vaccine made from the SV/69 strain of the Rhinopneumonia virus (RHIV), the bacteria strains of Salmonella abortus equi BN-12 - the causative agent of Salmonella abortion and Streptococcus equi N-34 - the causative agent of the horse strangles. Preclinical laboratory studies of the immunogenicity of the vaccine in linear and outbred mice showed that the preparation protects against experimental infection with the Rhinopneumonia virus by 88.8%, from the causative agents of Salmonella abortion and horse strangles by 100%. There were carried out clinical trials of a trivalent inactivated vaccine with a centrifuge strain Bacillus subtilis TNP-3 as an immunomodulator in order to specifically prevent salmonella abortion, rhinopneumonia and horse strangles. Clinical trials were carried out on horses in the Central regions of Yakutia. The business output of foals was 50.2% in the republic. The business yield in immunized mares was 76,0 % and in unvaccinated mares only 38,0 % in a controlled production trial at the "Uyruye" agricultural production complex. Consequently, immunization of mares with trivalent vaccine increased the reproduction rate by 38,0 %. Results of extensive production tests on 2,568 heads of herd horses confirmed the data of preclinical laboratory studies of immunogenicity in linear and outbred mice. The trivalent vaccine against rhinopneumonia, salmonella abortion and horse strangles stimulates immunobiological reactivity, induces the synthesis of specific antibodies in high titers and increases the business yield of foals from 18,0 to 38,0 %. The vaccine is highly effective and can provide recovery of disadvantaged settlements.