Adjuvanted Vaccine Research Articles

898. Influenza Surveillance in the US Veterans Health Administration (VHA): 2022-2023 Season

Abstract Background Influenza causes seasonal epidemics with substantial morbidity and mortality. Veterans Health Administration’s (VHA) large elderly population is at higher risk for influenza complications, including hospitalization, and death. Herein we summarize VHA’s national annual surveillance data for influenza activity and vaccinations. Methods Influenza-like-illness (ILI) as well as influenza-coded outpatient visits and hospitalizations, laboratory testing, and antivirals were obtained from VHA data sources (10/2/2022-4/22/23) and compared to prior years and CDC data. Vaccinations were captured starting 8/1/2022, with rates calculated based on VHA users in each fiscal year. Influenza RT-PCR positive respiratory samples underwent whole genome sequencing (WGS) to analyze clade and antiviral resistance. Results Surveillance metrics are presented (Table). Vaccinations were decreased compared to 2021-22, but the used of adjuvanted vaccine was increased. Weekly ILI ranged from 0.4%-1.4% in primary/urgent care settings. Activity was highest for 2022 Week 48, matching national influenza trends (Fig.1). Testing found 23,297 influenza positives of 457,020 tests performed (5.1%). Median length of stay (3 days) for hospitalized patients and deaths (127, 3%) were stable. Among 115 deaths where influenza type was available, 110 had Influenza A and 5 Influenza B. Following two low activity seasons, total influenza positives, outpatient visits, and hospitalizations during 2022-23 tracked closer to seasons prior to the COVID-19 pandemic (Table, Fig.2). 411 samples (in 16 states) were sequenced (410 Flu A: 136 H1, 274 H3; 1 B/Victoria), representing 12 subclades, which aligned with CDC reporting. No drug resistance mutations were found (Fig.3). Conclusion For 2022-23, influenza vaccinations in VHA dropped but percent vaccinated was stable. For the first time, over half of VHA-administered vaccines were adjuvanted formulation. The influenza season was notable for an earlier than usual peak (late Nov/early Dec), with overall increased activity compared to the prior two seasons. Testing for influenza during 2022-23 season was decreased but remained higher than pre-COVID-19 pandemic testing levels. VHA influenza activity and WGS analysis tracks closely with national CDC reporting. Disclosures All Authors: No reported disclosures

A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage

ABSTRACT The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.

Cost-effectiveness for high dose quadrivalent versus the adjuvanted quadrivalent influenza vaccine in the Italian older adult population.

To assess the cost-effectiveness of switching from adjuvanted quadrivalent vaccine (aQIV) to high-dose quadrivalent influenza vaccine (HD-QIV) in those aged ≥65 years from the Italian National Health Service perspective. We developed a decision tree model over a 1-year time-horizon to assess influenza-related costs and health outcomes. Two hospitalization approaches were considered: "hospitalization conditional on developing influenza" and "hospitalization possibly related to Influenza." The first approach considered only hospitalizations with influenza ICD-9-CM diagnosis codes. The second included hospitalizations for cardiorespiratory events possibly related to influenza to better capture the "hidden burden". Since comparative efficacy of high-dose quadrivalent influenza vaccine versus adjuvanted quadrivalent vaccine was lacking, we assumed relative efficacy versus a common comparator, standard-dose influenza quadrivalent vaccines (SD-QIV). We assumed the relative efficacy of HD-QIV vs. SD-QIV was 24.2 and 18.2% for the first and second hospitalization approaches, respectively, based on published information. Due to lack of comparative efficacy data for aQIV vs. SD-QIV, we assumed three different scenarios: 0, 6, and 12% relative efficacy in scenarios 1, 2, and 3, respectively. For the first hospitalization approach, HD-QIV was a cost-effective alternative to aQIV in all scenarios at a willingness-to-pay threshold of €30,000 per Quality Adjusted Life Years. The incremental cost-effectiveness ratios across the scenarios were €7,301, €9,805, and €14,733, respectively, much lower than the willingness-to-pay per Quality Adjusted Life Years threshold. For the second hospitalization approach, HD-QIV was a dominant alternative to aQIV across all scenarios. The robustness of the results was confirmed in one-way and probabilistic sensitivity analyses. Switching to HD-QIV from aQIV for the older adult in Italy would improve health-related outcomes, and would be cost-effective or cost saving.

COVID-19 update: New Novavax vaccine formulation for 2023-2024.

A new 2023-2024 formulation of the adjuvanted protein subunit COVID-19 vaccine manufactured by Novavax that was developed to more closely target currently circulating SARS-CoV-2 variants has been made available in the US under an FDA Emergency Use Authorization (EUA) for use in persons ≥12 years old. The original formulation of the Novavax vaccine is no longer authorized for use in the US. In September, updated formulations of the mRNA COVID-19 vaccines manufactured by Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) were licensed by the FDA for use in persons ≥12 years old and made available under EUAs for use in persons 6 months to 11 years old.

Examining the effectiveness and duration of adjuvanted vs. non-adjuvanted influenza vaccines in protecting older adults against symptomatic SARS-CoV-2 infection.

Annual influenza vaccination is one of the main public health measures able to drastically reduce the burden of this infectious disease. Some evidence suggests 'trained immunity' triggered by influenza vaccine might reduce the risk of SARS-CoV-2 infection. Adjuvanted influenza vaccines are known to induce a broader cross-reactive immunity. No studies investigated the effect of adjuvanted vs. non-adjuvanted influenza vaccines on the risk of symptomatic SARS-CoV-2 infection. A case-control analysis nested in a cohort of subjects aged ≥65 years and immunized with adjuvanted or non-adjuvanted influenza vaccines was conducted. Although no statistically significant (OR = 0.87; P = .082) difference between the two vaccine types was observed for the 9-month follow-up period, a 17% (OR = 0.83; P = .042) reduction in the odds of COVID-19 was observed for adjuvanted vaccines with a 6-month follow-up. Further evidence is needed, but these results might have implications given the complexity of the upcoming winter seasons, in which the co-occurrence of influenza, SARS-CoV-2 and other respiratory infections (e.g., syncytial virus) might be unpredictable.

Recent advance in the development of tuberculosis vaccines in clinical trials and virus-like particle-based vaccine candidates.

Tuberculosis (TB) remains a serious public health threat around the world. An effective vaccine is urgently required for cost-effective, long-term control of TB. However, the only licensed vaccine Bacillus Calmette-Guerin (BCG) is limited to prevent TB for its highly variable efficacy. Substantial progress has been made in research and development (R&D) of TB vaccines in the past decades, and a dozen vaccine candidates, including live attenuated mycobacterial vaccines, killed mycobacterial vaccines, adjuvanted subunit vaccines, viral vector vaccines, and messenger RNA (mRNA) vaccines were developed in clinical trials to date. Nevertheless, many challenges to the successful authorization for the use and deployment of an effective tuberculosis vaccine remain. Therefore, it is still necessary and urgent to continue exploring new vaccine construction approaches. Virus-like particles (VLPs) present excellent prospects in the field of vaccine development because of their helpful immunological features such as being safe templates without containing viral nucleic acid, repetitive surface geometry, conformational epitopes similar to natural viruses, and enhancing both innate and adaptive immune responses. The marketization process of VLP vaccines has never stopped despite VLP vaccines face several shortcomings such as their complex and slow development process and high production cost, and several VLP-based vaccines, including vaccines against Human papillomavirus (HPV), Hepatitis B Virus (HBV) and malaria, are successfully licensed for use at the market. In this review, we provide an update on the current progress regarding the development of TB vaccines in clinical trials and seek to give an overview of VLP-based TB vaccine candidates.

Adjuvant Human Papillomavirus Vaccination After Excisional Procedure for Cervical Intraepithelial Neoplasia, A Cost-effectiveness Analysis

(Abstracted from Obstet Gynecol 2023;141:756–763) A precursor to one of the most common cancers in the world and the United States and worldwide (cervical malignancy) is cervical intraepithelial neoplasia (CIN). Because the causal agent is known to be human papillomavirus (HPV), a primary prevention method of HPV vaccination is universally recommended for individuals 9 to 26 years of age and is not universally recommended but is approved for individuals aged 27 to 45 years.

Evaluating risk of bias using ROBINS-I tool in nonrandomized studies of adjuvanted influenza vaccine

Seasonal variation in influenza vaccine effectiveness (VE) makes real-world evidence (RWE) useful in supplementing the clinical-evidence base from randomized clinical trials. Adjuvanted inactivated influenza vaccine (aIIV) VE has been evaluated in multiple nonrandomized RWE studies. A systematic literature review of RWE studies evaluating the absolute or relative VE of aIIV was conducted. Identified studies were assessed by evaluators for risk of bias (RoB) by means of the ROBINS-I (Reduction of Bias In Non-randomized Studies of Interventions) tool to inform evidence-based medicine deliberations. Differences in evaluator assessments were resolved by consensus. The literature review yielded 14 follow-up studies, seven test-negative case-control (TNCC) studies, five traditional case-control studies, and one cluster-randomized clinical trial. Most follow-up studies and three TNCC studies were judged at low RoB. Issues increasing RoB included inadequate control of confounding, selection of controls, and reliance on recall of vaccination. The concerns identified in any of the designs could be mitigated with straightforward revisions to design or implementation. 17 of 27 nonrandomized studies of adjuvanted influenza-vaccine effectiveness, some from each of four study designs, were judged at low risk of material bias. These studies merit credence in assessing aIIV effectiveness relative to other influenza vaccines.

Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms

Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q)and optionally a synthetic TLR4 agonist (M). Two R21 vaccine formulations, R21/LMQ and R21/SQ, offer the highest protection (81%-100%), yet they trigger different innate sensing mechanisms in macrophages with LMQ, but not SQ, activating the NLRP3 inflammasome. The resulting invivo adaptive responses have a different TH1/TH2 balance and engage divergent innate pathways while retaining high protective efficacy. We describe how modular changes in vaccine formulation allow for the dissection of the underlying immune pathways, enabling future mechanistically informed vaccine design.

The Real-World Study of Immunogenicity and Safety of the Adjuvant Recombinant Vaccine against Varicella Zoster Virus in Patients with Immune-Mediated Inflammatory Diseases Treated with Janus Kinase Inhibitors.

Background. The risk of herpes zoster reactivation is increased in immunocompromised patients, especially in those with immune-mediated inflammatory diseases (IMIDs) on Janus kinase inhibitor (JAKi) treatment. The recombinant subunit herpes zoster vaccine (RZV) is a non-live vaccine, recently approved for this subgroup of patients, which shows high rates of vaccine effectiveness, with few adverse effects reported in clinical trials. Purpose. The aim of this real-world study was to determine the immunogenicity and safety of RZV in IMID patients on JAKi treatment. Methods. The increase in the concentration of anti-gE antibody for varicella zoster virus post-vaccination, compared to the pre-vaccination concentration, was analyzed to test the humoral immune response. Adverse effects after the first and second vaccine doses were registered. Results. In total, 49 patients were analyzed, and a fourfold increase in antibody concentration was achieved in almost 40% of subjects, with only one serious local adverse effect. Discussion. The resulting immunogenicity was lower than that observed in clinical trials, probably due to the presence of immune disease and immunosuppressive treatment, and to the fact that this was a real-world study. No differences in response according to age, previous virus zoster reactivation, or concomitant treatments were found. Conclusions. RZV was well tolerated and reached the immune response objective in 40% of patients. These results reinforce the importance of including RZV vaccination for immunosuppressed patients. Real-world studies regarding vaccine effectiveness are still needed in order to gain a full understanding of the response to RZV in this group of patients.

Development of a multivalent adjuvanted inactivated vaccine against variant arthrotropic avian reoviruses.

Variant avian reoviruses (ARVs) are economically important emerging pathogens of poultry, which mainly affect young broiler chickens and cause significant production losses. Currently, there are no effective commercial vaccines available for control and prevention of emerging variant ARVs. In this study, monovalent inactivated adjuvated (20% Emulsigen D) broiler breeder vaccines containing antigens from ARV genotype cluster (C) group -2, -4, -5, or -6, and a multivalent vaccine containing antigens from all the four indicated genotypic cluster groups were developed and evaluated for their efficacy in protecting broiler progenies against homologous or heterologous ARV challenge. The use of monovalent or multivalent inactivated vaccines in a prime-boost immunization strategy induced the production of ARV specific antibodies in broiler breeders. The maternal antibodies were effectively transferred to broiler progenies. Broiler progenies obtained from immunized breeders demonstrated milder clinical symptoms and reduced gross and histopathological lesions after homologous ARV challenge. More severe gross and histological lesions were observed in challenged progenies from unvaccinated broiler breeders. However, cross protection was not observed when either of the monovalent-vaccine groups were challenged with a heterologous virus. In addition, the progenies from the unvaccinated ARV challenged control or heterologous ARV challenged vaccinated groups had significantly reduced body weight gain (p < 0.01) than the unchallenged-control, challenged-multivalent, or homologous ARV-challenged monovalent vaccine groups. However, homologous ARV challenged progenies in the multivalent or monovalent vaccine groups had similar body weight gain as the control unchallenged group with significantly reduced viral load (p < 0.01) in the gastrocnemius tendon tissue. This study indicates that broad-spectrum protection of broiler progenies from variant ARV infections is feasible through the development of multivalent vaccines after proper characterization, selection and incorporation of multiple antigens based on circulating ARV genotypes in targeted regions.

Determining the protective effect of a boron adjuvanted vaccine with an experimental infection model in mice

Determining the protective effect of a boron adjuvanted vaccine with an experimental infection model in mice

Expression of Toll-like Receptors on the Immune Cells in Patients with Common Variable Immune Deficiency after Different Schemes of Influenza Vaccination.

for the first time, the effect of one and two doses of adjuvanted influenza vaccines on toll-like receptors (TLRs) in patients with common variable immunodeficiency (CVID) was studied and compared (primary vaccination with one vs. two doses, primary vs. repeated vaccination). Six patients received one dose of quadrivalent adjuvanted influenza vaccine during the 2018-2019 and 2019-2020 influenza seasons, and nine patients with CVID received two doses of trivalent inactivated influenza vaccine during 2019-2020. Expression of TLRs was measured by flow cytometry. The expression of toll-like receptors in patients with CVID was noted both with repeated (annual) administration of the influenza vaccine and in most cases was accompanied by an increase in the proportion of granulocytes (TLR3 and TLR9), lymphocytes (TLR3 and TLR8), and monocytes (TLR3 and TLR9). When carried out for the first time as a simultaneous vaccination with two doses it was accompanied by an increase in the proportion of granulocytes, lymphocytes expressing TLR9, and on monocytes-TLR3 and TLR9. in CVID patients, the use of adjuvanted vaccines is promising, and research on the influence of the innate immunity and more effective regimens should be continued.

Tetravalent SARS-CoV-2 S1 subunit protein vaccination elicits robust humoral and cellular immune responses in SIV-infected rhesus macaque controllers.

The study provides important insights into the immunogenicity and efficacy of a tetravalent protein subunit vaccine candidate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine induced both humoral and cellular immune responses in nonhuman primates with controlled SIVagm infection and was able to generate Omicron variant-specific antibodies without specifically vaccinating with Omicron. These findings suggest that the tetravalent composition of the vaccine candidate could provide broad protection against multiple SARS-CoV-2 variants while minimizing the risk of immune escape and the emergence of new variants. Additionally, the use of rhesus macaques with controlled SIVsab infection may better represent vaccine immunogenicity in humans with chronic viral diseases, highlighting the importance of preclinical animal models in vaccine development. Overall, the study provides valuable information for the development and implementation of coronavirus disease 2019 vaccines, particularly for achieving global vaccine equity and addressing emerging variants.

Toll-like Receptor Ligands Enhance Vaccine Efficacy against a Virulent Newcastle Disease Virus Challenge in Chickens.

To enhance the efficacy of the current Newcastle disease vaccine, we have selected potential adjuvants that target well-characterized pattern recognition receptors: the toll-like receptors (TLRs). Imiquimod is a small-molecule activator of TLR7, which is a sensor of dsDNA. ODN-1826 is a mimetic of CpG DNA and ligates TLR21 (a chicken homologue of TLR9 in mammals). The activation of TLRs leads to antiviral responses, including the induction of type I interferons (IFNs). In this study, birds were vaccinated intranasally with a live LaSota strain with or without imiquimod or ODN-1826 (50 µg/bird). Two weeks after vaccination, the birds were challenged with a virulent Newcastle disease virus (chicken/CA/212676/2002). Both adjuvants (imiquimod or ODN-1826) induced higher and more uniform antibody titers among vaccinated birds compared with the live vaccine-alone group. In addition, adjuvanted vaccines demonstrated greater protective efficacy in terms of the reduction in virus-shedding titer and the number of birds shedding the challenge virus at 2 and 4 days post-challenge. A differential expression of antiviral and immune-related genes was observed among groups from tissues (Harderian gland, trachea, cecal tonsil, and spleen) collected 1 and 3 days after treatment. These results demonstrate the potential of TLR-targeted adjuvants as mucosal vaccine enhancers and warrant a further characterization of immune correlates and optimization for efficacy.

Adjuvantation of whole-killed Leishmania vaccine with anti-CD200 and anti-CD300a antibodies potentiates its efficacy and provides protection against wild-type parasites

One of the major reasons behind the limited success of vaccine candidates against all forms of leishmaniasis is the inability of parasitic antigens to induce robust cell-mediated immunity and immunological memory. Here we find, for the first time, that the adjuvantation of whole-killed Leishmania vaccine (Leishvacc) with anti-CD200 and anti-CD300a antibodies enhances CD4+ T cells mediated immunity in vaccinated mice and provides protection against wild-type parasites. The antibody adjuvantation, either alone or with a TLR4 agonist monophosphoryl A (MPL-A), induced the production of pro-inflammatory cytokines viz., IFN-γ, TNF-α, and IL-2 by antigen experienced CD4+ T cells, and also enhanced their rate of conversion into their memory phenotypes against Leishvacc antigens. The antibody adjuvanted vaccine also promoted the generation of IgG2a-mediated protective humoral immunity in vaccinated mice. Further, the mice vaccinated with antibodies adjuvanted vaccine showed strong resilience against metacyclic forms of L. donovani parasites as we observed reduced clinical features such as splenomegaly, hepatomegaly, granulomatous tissues in the liver, and parasitic load in their spleen. The findings of this study demonstrate that the anti-CD200 and anti-CD300a antibodies have potential to increase the protective efficacy of the whole-killed Leishmania vaccine, and opens up a new gateway to diversify the roles of immune checkpoints in vaccine development against leishmaniasis.

The Impact of Adjuvanted Influenza Vaccine on Disease Severity in the US: A Stochastic Model.

Influenza can exacerbate underlying medical conditions. In this study, we modelled the potential impact of an egg-based quadrivalent influenza vaccine (QIVe) or adjuvanted QIV (aQIV) on hospitalizations and mortality from influenza-related cardiovascular disease (CVD), respiratory, and other complications in adults ≥65 years of age in the US with underlying chronic conditions. We used a stochastic decision-tree model, with 1000 simulations varying input across predicted ranges. Due to the variable nature of influenza across seasons and differences in published estimates for input parameters, data are presented as 95% confidence intervals. Compared with no vaccination, use of aQIV would prevent 135,450-564,360 hospitalizations and 1612-29,226 deaths across outcomes evaluated. Overall, aQIV prevented 1071-18,388 more hospitalizations and 85-1944 more deaths than QIVe. By routine seasonal vaccination against influenza, a substantial number of severe influenza-associated complications and deaths, caused by direct influenza symptoms or by exacerbation of chronic conditions, can be prevented in high-risk adults ≥65 years of age in the US.

Immunogenicity and Safety of MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared with a Nonadjuvanted, Quadrivalent Influenza Vaccine in Adults 50-64 Years of Age.

Adults aged 50-64 years have a high incidence of symptomatic influenza associated with substantial disease and economic burden each year. We conducted a randomized, controlled trial to compare the immunogenicity and safety of an adjuvanted quadrivalent inactivated influenza vaccine (aIIV4; n = 1027) with a nonadjuvanted standard dose IIV4 (n = 1017) in this population. Immunogenicity was evaluated on Days 22, 181, and 271. On Day 22, upper limits (UL) of 95% confidence intervals (CI) for geometric mean titer (GMT) ratios (IIV4/aIIV4) were <1.5 and 95% CI ULs for the difference in seroconversion rate (SCR IIV4 - aIIV4) were <10% for all four vaccine strains, meeting primary endpoint noninferiority criteria. Protocol-defined superiority criteria (95% CI ULs < 1.0) were also met for A(H1N1) and A(H3N2). Immune responses following aIIV4 vaccination were more pronounced in persons with medical comorbidities and those not recently vaccinated against influenza. Safety data were consistent with previous studies of MF59 adjuvanted seasonal and pandemic influenza vaccines. These findings support the immunological benefit of aIIV4 for persons aged 50-64 years, especially those with comorbidities.

Development of B-cell response during immunization with inactivated influenza vaccines "Grippol plus", "Sovigripp" and "Ultrix"

The worldwide circulating influenza viruses annually lead to serious medical and socio-economic consequences. It is generally recognized that vaccination is the most effective and safe strategy for preventing influenza and its complications. In order to reduce side effects when using live viruses, split and subunit influenza vaccines are widely used. To date, the characteristics of B cell response after immunization with influenza vaccines remain insufficiently studied. The aim of our study was to compare the effects of immunization with different influenza vaccines, i.e., “Sovigripp”, “Grippol plus” and “Ultrix”, on the B cell response. The study was conducted on the base of Clinical Department at the A.Smorodintsev Influenza Research Institute during the epidemic flu season of 2018-2019. For clinical studies, venous blood samples were obtained from 39 volunteers before vaccination, on the 7th and 21st days after vaccination. The subpopulations of B cells were analyzed by flow cytometry using fluorescently labeled antibodies to CD3, CD19, CD20, CD27, CD38, IgD, IgA surface antigens (BioLegend, USA). Cryopreserved mononuclear cells (1 × 106 cells/sample) were used for analysis. The processing of flow cytometry data was carried out with special software (H., Cytexpert, Beckman Coulter, Inc., USA) and Kaluza 2.0 (Beckman Coulter, Inc., USA). The differences with pre-vaccination data were evaluated using the Mann–Whitney U-test and being considered significant at p &lt; 0.05. As a result of the studies, the following subpopulations of B lymphocytes (CD3-CD19+) were specified: naive B cells (CD20+CD27-IgD+), non-switched memory B cells (CD20+CD27+IgD+), switched memory B cells (CD20+CD27+IgD-), effector memory B cells (CD20+CD27-IgD-), plasmablasts (CD20-CD38hiCD27hi). Activation of the B cell immune response was assessed by measuring the relative content of CD38+B cells belonging to subpopulations of naive, effector B lymphocytes, switched and non-switched memory B cells. The analysis of B cell response showed an increase in both the total number of B lymphocytes and their subpopulations including plasmablasts and activated switched memory B cells after immunization. With adjuvant vaccines “Grippol plus” and “Sovigripp”, as compared with the split “Ultrix” vaccine, an early increase in relative counts of plasmablasts was shown on the 7th day of the study. At the same time, all three vaccines equally contributed to an increase in the number of activated memory B cells with a switched antibody isotype. Thus, the assessment of B cell response revealed significant changes in contents of peripheral blood B cell subpopulations in response to vaccination with “Grippol plus”, “Sovigripp”, or “Ultrix”.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)

BackgroundInfluenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. MethodsA test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). ResultsOf 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%–51.1%) for naTIV and 53.5% (42.8%–62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%–66.8%) for aTIV and 44.8% (39.1%–50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61–0.92), demonstrating statistically significant benefit favoring aTIV. ConclusionsAdjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.