Recombinant Influenza Vaccine Research Articles

Chimeric Virus-like Particles of Physalis Mottle Virus as Carriers of M2e Peptides of Influenza a Virus.

Plant viruses and virus-like particles (VLPs) are safe for mammals and can be used as a carrier/platform for the presentation of foreign antigens in vaccine development. The aim of this study was to use the coat protein (CP) of Physalis mottle virus (PhMV) as a carrier to display the extracellular domain of the transmembrane protein M2 of influenza A virus (M2e). M2e is a highly conserved antigen, but to induce an effective immune response it must be linked to an adjuvant or carrier VLP. Four tandem copies of M2e were either fused to the N-terminus of the full-length PhMV CP or replaced the 43 N-terminal amino acids of the PhMV CP. Only the first fusion protein was successfully expressed in Escherichia coli, where it self-assembled into spherical VLPs of about 30 nm in size. The particles were efficiently recognized by anti-M2e antibodies, indicating that the M2e peptides were exposed on the surface. Subcutaneous immunization of mice with VLPs carrying four copies of M2e induced high levels of M2e-specific IgG antibodies in serum and protected animals from a lethal influenza A virus challenge. Therefore, PhMV particles carrying M2e peptides may become useful research tools for the development of recombinant influenza vaccines.

Summary of the National Advisory Committee on Immunization (NACI) Supplemental Guidance on Influenza Vaccination in Adults 65 Years of Age and Older.

Adults 65 years of age and older are at higher risk of influenza complications, such as hospitalization and death. As a result, seasonal influenza immunization is particularly important for this group. This supplemental statement provides an evidence summary on the preferential use of one or more of the age-appropriate influenza vaccines for adults 65 years of age and older, over other age-appropriate influenza vaccines. The National Advisory Committee on Immunization (NACI)'s Influenza Working Group undertook an overview of existing systematic reviews on the efficacy, effectiveness, safety and cost effectiveness of influenza vaccination in adults 65 years of age and older. Additionally, NACI's evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings and apply an ethics, feasibility and acceptability lens to develop recommendations. The evidence suggests that high-dose inactivated influenza vaccine (IIV-HD), adjuvanted inactivated influenza vaccine (IIV-Adj) and recombinant influenza vaccine (RIV) offer increased benefits for adults 65 years of age and older when compared to standard dose influenza vaccines. The IIV-HD had the most supporting evidence, followed by IIV-Adj and then RIV. Evidence comparing these enhanced vaccines was limited. Following a thorough review of the complete body of evidence, NACI recommends that IIV-HD, IIV-Adj or RIV should be offered over other influenza vaccines for adults 65 years of age and older. NACI also continues to strongly recommend the inclusion of adults 65 years of age and older among those for whom it is particularly important to receive influenza vaccination.

Summary of the National Advisory Committee on Immunization (NACI) Seasonal Influenza Vaccine Statement for 2024-2025.

The National Advisory Committee on Immunization (NACI) reviews the evolving evidence on influenza immunization and provides annual recommendations regarding the use of seasonal influenza vaccines. The NACI Statement on Seasonal Influenza Vaccine for 2024-2025 updates the NACI recommendations from the previous year. To summarize the 2024-2025 NACI seasonal influenza vaccine recommendations and to highlight new and updated information. For the development of the Statement on Seasonal Influenza Vaccine for 2024-2025, the NACI Influenza Working Group applied the NACI evidence-based process to assess available evidence and formulate recommendations. These recommendations underwent a thorough evaluation and were approved by NACI based on the available evidence. Key updates for the 2024-2025 influenza season include updated immunization recommendations reflecting changes in influenza epidemiology and revised guidance for vaccine administration during pregnancy and in older adults. The National Advisory Committee on Immunization recommends that any age-appropriate quadrivalent or trivalent influenza vaccine should be used for individuals six months of age and older who do not have contraindications or precautions. NACI reaffirms the importance of influenza vaccination with inactivated or recombinant influenza vaccines in pregnancy. Finally, NACI recommends that inactivated high-dose (IIV-HD), inactivated adjuvanted (IIV-Adj) or recombinant influenza vaccine (RIV) should be offered, when available, over other influenza vaccines for adults 65 years of age and older.

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.

Randomised immunogenicity trial comparing 2019-2020 recombinant and egg-based influenza vaccines among frequently vaccinated healthcare personnel in Israel

ObjectivesTrivalent inactivated influenza vaccine effectiveness was low in a prospective cohort of healthcare personnel (HCP) in Israel from 2016 to 2019. We conducted a randomised immunogenicity trial of quadrivalent recombinant influenza vaccine (RIV4) and standard-dose inactivated influenza vaccine (IIV4) among frequently and infrequently vaccinated previous cohort participants. MethodsFrom October 2019 to January 2020, we enrolled and randomly allocated HCP from two Israeli hospitals to receive IIV4 or RIV4. Hemagglutination inhibition (HAI) antibody titres against 2019-2020 vaccine reference influenza viruses were compared between vaccine groups using geometric mean titre (GMT) ratios from sera collected one-month post-vaccination and by frequency of vaccination in the past 5 years (>2 vs ≤2). ResultsAmong 415 HCP, the GMT ratio comparing RIV4 to IIV4 was 2.0 (95% confidence interval [CI] 1.7-2.7) for A(H1N1)pdm09, 1.6 (95% CI: 1.3-1.9) for A(H3N2), 1.8 (95% CI: 1.4-2.2) for B(Yamagata), and 1.1 (95% CI: 0.9-1.4) for B(Victoria). Similarly, RIV4 elicited higher HAI titres than IIV4 against all 2019-2020 vaccine reference viruses except B(Victoria) among infrequently and frequently vaccinated HCP (lower bound of GMT ratio 95% CIs ≥1.0). ConclusionRIV4 had improved immunogenicity for influenza vaccine strains among both infrequent and frequent vaccinees compared to standard-dose IIV4. Clinical trials registrationNCT04523324

A Rapid Virus-Free Method for Producing Influenza HA Immunogen Needed for Preparation of Influenza Vaccine Potency Antisera Reagents.

The potency of inactivated and recombinant influenza vaccines is measured using the single-radial immunodiffusion (SRID) assay. The strain-specific antigen and antibody potency reagents required for the assay are prepared and distributed by regulatory agencies to ensure vaccine standardization, but timely reagent production is always challenging. This poses unique concerns for rapid pandemic responses. Alternative methods have been described for generating strain-specific potency antibody reagents without the need for live influenza virus, but such methods are infrequently used, suggesting the need for additional antigen expression approaches. We describe a rapid process using a mammalian expression system to produce recombinant influenza hemagglutinin (rHA). This platform was used to generate rHA from two H5 clade 2.3.4.4 influenza viruses, in both soluble ectodomain or full-length HA forms, and a soluble ectodomain rHA from an influenza H2 virus. The purified rHAs were used as immunogens to produce HA antibody reagents that were tested for suitability in the SRID assay to accurately measure the potency of inactivated pandemic influenza vaccines. Antibody reagents generated to either ectodomain or full-length rHA worked well in the SRID assay and resulted in vaccine potency values equivalent to those generated with standard reference antibodies. The results demonstrate that rHA produced from a simple mammalian cell transfection method can be used to generate HA antibody suitable for use in the influenza vaccine SRID potency assay and suggest a practical means by which an extensive library of pandemic reagents can easily be prepared in advance of and during an influenza emergency.

Pichia pastoris an Ideal Host for the Production of Recombinant Influenza Vaccines

Pichia pastoris is a methylotrophic yeast with remarkable characteristics such as lacking endotoxin, producing high amounts of recombinant protein, performing post-translational modifications, and so on. Influenza A virus, a member of the Orthomyxoviridae family, is the cause of avian influenza. Three avian influenza virus subtypes, H5, H7 and H9, are commercially and physiologically significant in the poultry industry. Some researchers considered influenza to be the next pandemic disease. Nowadays, researchers have paid attention to producing novel and effective recombinant vaccines, especially in the poultry industry. Due to the advantages of P. pastoris yeast, it can be used as an ideal expression system for producing subunit vaccines. Although several studies have been conducted in this field, there is no comprehensive review of using P. pastoris to produce recombinant influenza vaccines. This review explains the different strains, phenotypes, and advantages of this yeast and then the production of recombinant influenza vaccines using this expression system is discussed in detail.

Safety of quadrivalent recombinant influenza vaccine in pregnant persons and their infants

BackgroundThe Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that all pregnant persons receive any licensed, recommended, and age-appropriate inactivated influenza vaccine (SD-IIV) or recombinant influenza vaccine (RIV) to protect against influenza and influenza-related complications. RIV was safe and efficacious in pre- and postlicensure studies, however there is limited RIV safety data in pregnant persons. ObjectiveTo evaluate the safety of quadrivalent recombinant influenza vaccine (RIV4) versus a quadrivalent standard-dose, inactivated influenza (SD-IIV4) in a large cohort of pregnant persons and their infants. Study DesignThis postlicensure observational safety study conducted at Kaiser Permanente Northern California evaluated the subset of pregnant persons vaccinated in routine care as part of a larger cluster-randomized vaccine effectiveness study comparing RIV4 vs. SD-IIV4 (ClinicalTrials.gov NCT03694392). We identified pregnancy (spontaneous abortion, preterm labor, stillbirth/fetal death, congenital/fetal anomalies detected during pregnancy, eclampsia/pre-eclampsia, placental abruption), birth (preterm birth, low birth weight, small for gestational age), and neonatal/infant outcomes (infant death, failure to thrive, congenital anomalies detected after delivery) using diagnostic codes among pregnant persons ≥18 years immunized with RIV4 or SD-IIV4 during the 2018/19 and 2019/20 influenza seasons and their infants. We used conditional logistic regression adjusted for age group, race, ethnicity, trimester of influenza vaccination, comorbidities, and BMI, stratified by gestational age to estimate the odds ratio (OR) of pregnancy outcomes following vaccination with RIV4 vs. SD-IIV4. Using logistic regression, we separately estimated the adjusted OR of birth and neonatal/infant outcomes in the first year of life (eg, death) in infants of RIV4 vs. SD-IIV4 vaccinated pregnant persons. ResultsThe study population included 48,781 pregnant persons (RIV4 = 14,981; SD-IIV4 = 33,800) and 47,394 live births (RIV4 = 14,538; SD-IIV4 = 32,856). There was no statistical difference in any pregnancy outcome or in birth and neonatal/infant outcome between RIV4 vs. SD-IIV4 vaccinated pregnant persons and their infants. ConclusionCompared with receipt of a SD-IIV4 during pregnancy, this large study did not identify any pregnancy, birth, or neonatal/infant safety concerns following receipt of a RIV4 during pregnancy and demonstrates that the safety of RIV4 in pregnancy was similar to SD-IIV4. This study provides additional evidence regarding the safety of influenza vaccination in pregnant persons and further supports ACIP and ACOG recommendations that all pregnant persons receive an inactivated or recombinant influenza vaccine.

Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis.

Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

Trivalent and quadrivalent seasonal influenza vaccine in adults aged 60 and older: a systematic review and network meta-analysis

ObjectivesTo compare the efficacy of influenza vaccines of any valency for adults 60 years and older.Design and settingSystematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE,...

Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults

ABSTRACT The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018–19 and 2019–20 seasons to compare immunogenicity of sequential vaccination. Participants 18–64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018–19; 332 were revaccinated in 2019–20. In 2018–19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019–20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018–19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.

Cost-effectiveness of recombinant influenza vaccine compared with standard dose influenza vaccine in adults 18–64 years of age

BackgroundThe Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP’s preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults. MethodsWe used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18–64 years old. Model inputs included 2018–2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019–2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season. ResultsAmong adults ages 18–64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50–64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18–64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18–64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50–64-year-olds. ConclusionsWhile RIV4 was effective and cost-effective relative to SD-IIV4 for both 50–64-year-old and 18–64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18–64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50–64 year olds) to maximize their cost-benefit ratios.

Non-neutralizing immune-mediated cross-protection against influenza viruses by chimeric M2e-H3 stalk protein or multi-subtype neuraminidase plus M2e virus-like particle vaccine in ferrets

Abstract Current influenza vaccine based on hemagglutinin (HA) immunity is not effective in providing cross protection against circulating variants and new pandemic viruses. In prior studies, we developed universal influenza vaccine candidates of multi-subtype neuraminidase and M2 ectodomain virus-like particles (m-cNA-M2e VLP) and chimeric M2e-H3 stalk protein vaccine (M2e-H3stalk), which were effective in inducing cross-protective immunity in mice. Here, we evaluated the immunogenicity and efficacy of these recombinant universal influenza vaccines in ferrets. Our results showed that immunization of ferrets with recombinant universal vaccines induced high levels of IgG antibody responses (M2e, H3stalk, multi-subtype NA), NA inhibition (NAI), antibody-secreting plasma cells in spleens, and IFN-γ secreting blood mononucleate cells. Ferrets with either m-cNA-M2e VLP or M2e-H3stalk vaccine were moderately protected from H1N1 and H3N2 influenza viruses as evidenced by lower viral titers in nasal washes, trachea and lung after challenge. Tests of passive immunity of vaccinated ferret antisera indicate that multi-NA plus M2e vaccine conferred more effective and broader humoral immunity in naïve mice than M2e-H3stalk vaccine. Our findings support that immunity to M2e, HA-stalk, and multi subtypes NA will induce broader cross protection in ferrets, which is likely translational to humans.

Summary of the National Advisory Committee on Immunization (NACI) Updated Guidance on Influenza Vaccination During Pregnancy.

Seasonal influenza infection can lead to serious complications and adverse outcomes for pregnant individuals, the developing fetus and infants younger than six months of age. This supplemental statement provides an evidence summary on the safety and effectiveness of influenza vaccination in pregnant individuals, and the benefits and risks to the pregnant person, the developing fetus and infants younger than six months of age. A systematic review was conducted on the effectiveness and safety of influenza vaccination in pregnancy. The National Advisory Committee on Immunization (NACI)'s evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. The evidence suggests that influenza vaccination during pregnancy is effective in reducing the risk of laboratory-confirmed influenza infection and hospitalization in both pregnant individuals and their infants up to six months postpartum. The evidence also suggests that influenza vaccination during pregnancy does not increase the risk of non-obstetric serious adverse events in pregnant persons, infant death, spontaneous abortion, stillbirth, preterm birth, small for gestational age, low birth weight and congenital anomalies. Based on this body of evidence, NACI reaffirms the safety and importance of influenza vaccination during pregnancy. NACI recommends that individuals at any stage of pregnancy should receive an age-appropriate inactivated, unadjuvanted or recombinant influenza vaccine each influenza season. Influenza vaccination may be given at the same time as, or at any time before or after administration of another vaccine, including the coronavirus disease 2019 (COVID-19) or pertussis vaccines.

Immunogenicity of Enhanced Influenza Vaccines Against Mismatched Influenza Strains in Older Adults: A Review of Randomized Controlled Trials.

Antigenic drift is a major driver of viral evolution and a primary reason why influenza vaccines must be reformulated annually. Mismatch between vaccine and circulating viral strains negatively affects vaccine effectiveness and often contributes to higher rates of influenza-related hospitalizations and deaths, particularly in years dominated by A(H3N2). Several countries recommend enhanced influenza vaccines for older adults, who are at the highest risk of severe influenza complications and mortality. The immunogenicity of enhanced vaccines against heterologous A(H3N2) strains has been examined in nine studies to date. In six studies, an enhanced, licensed MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) consistently increased heterologous antibody titers relative to standard influenza vaccine, with evidence of a broad heterologous immune response across multiple genetic clades. In one study, licensed high-dose trivalent inactivated influenza vaccine (HD-IIV3) also induced higher heterologous antibody titers than standard influenza vaccine. In a study comparing a higher dose licensed quadrivalent recombinant influenza vaccine (RIV4) with HD-IIV3 and aIIV3, no significant differences in antibody titers against a heterologous strain were observed, although seroconversion rates were higher with RIV4 versus comparators. With the unmet medical need for improved influenza vaccines, the paucity of studies especially with enhanced vaccines covering mismatched strains highlights a need for further investigation of cross-protection in older adults.

재조합 인플루엔자 백신과 불활성화 인플루엔자 백신의 면역원성 비교

To compare surrogate markers of immunogenicity between recombinant and inactivated influenza vaccines, this study conducted a systematic review and meta-analysis for each strain. Three databases of Medline (Pubmed), Embase and Cochrane Central were searched to identify all published literature up to July 2023. Out of a total of 1,658 initially identified articles, 14 randomized controlled trials were selected based on inclusion and exclusion criteria. The program R version 4.3.1 was used to estimate the mean difference of geometric mean titer (GMT) and the pooled risk ratio (RR) of seroconversion and seroprotection with 95% confidence intervals. The meta-analysis results found higher GMT effect sizes for recombinant influenza vaccines compared to inactivated vaccines for A/H3N2 (MD=124.87, 95% CI 52.63-197.11) and B/Yamagata (MD=19.89, 95% CI 7.61-32.17) strains. In terms of seroconversion rates, recombinant influenza vaccines exhibited higher seroconversion for A/H3N2 (RR=1.33, 95% CI 1.26-1.40) and B/Yamagata (RR=1.75, 95% CI 1.06-2.89) strains. Slightly higher seroprotection rates were observed for A/H3N2 (RR=1.04, 95% CI 1.02-1.07) and B/Yamagata (RR=1.07, 95% CI 1.01-1.13) strains with recombinant vaccines. The findings from this study contribute valuable evidence for regulatory decisions when introducing recombinant vaccines in South Korea.

Adjuvanted nanoliposomes displaying six hemagglutinins and neuraminidases as an influenza virus vaccine

Inclusion of defined quantities of the two major surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA), could benefit seasonal influenza vaccines. Recombinant HA and NA multimeric proteins derived from three influenza serotypes, H1N1, H3N2, and type B, are surface displayed on nanoliposomes co-loaded with immunostimulatory adjuvants, generating "hexaplex" particles that are used to immunize mice. Protective immune responses to hexaplex liposomes involve functional antibody elicitation against each included antigen, comparable to vaccination with monovalent antigen particles. When compared to contemporary recombinant or adjuvanted influenza virus vaccines, hexaplex liposomes perform favorably in many areas, including antibody production, Tcell activation, protection from lethal virus challenge, and protection following passive sera transfer. Based on these results, hexaplex liposomes warrant further investigation as an adjuvanted recombinant influenza vaccine formulation.

Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines

Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018−19 (N = 723) and 2019−20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.

Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age

BackgroundQuadrivalent recombinant influenza vaccines contain three times the amount of hemagglutinin protein as standard-dose egg-based vaccines, and the recombinant formulation is not susceptible to antigenic drift during manufacturing. Data are needed on the relative effectiveness of recombinant vaccines as compared with standard-dose vaccines against influenza-related outcomes in adults under the age of 65 years.MethodsIn this cluster-randomized observational study, Kaiser Permanente Northern California facilities routinely administered either a high-dose recombinant influenza vaccine (Flublok Quadrivalent) or one of two standard-dose influenza vaccines during the 2018–2019 and 2019–2020 influenza seasons to adults 50 to 64 years of age (primary age group) and 18 to 49 years of age. Each facility alternated weekly between the two vaccine formulations. The primary outcome was influenza (A or B) confirmed by polymerase-chain-reaction (PCR) testing. Secondary outcomes included influenza A, influenza B, and influenza-related hospitalization outcomes. We used Cox regression analysis to estimate the hazard ratio of the recombinant vaccine as compared with the standard-dose vaccines against each outcome. We calculated the relative vaccine effectiveness as 1 minus the hazard ratio.ResultsThe study population included 1,630,328 vaccinees between the ages of 18 and 64 years (632,962 in the recombinant-vaccine group and 997,366 in the standard-dose group). During this study period, 1386 cases of PCR-confirmed influenza were diagnosed in the recombinant-vaccine group and 2435 cases in the standard-dose group. Among the participants who were 50 to 64 years of age, 559 participants (2.00 cases per 1000) tested positive for influenza in the recombinant-vaccine group as compared with 925 participants (2.34 cases per 1000) in the standard-dose group (relative vaccine effectiveness, 15.3%; 95% confidence interval [CI], 5.9 to 23.8; P=0.002). In the same age group, the relative vaccine effectiveness against influenza A was 15.7% (95% CI, 6.0 to 24.5; P=0.002). The recombinant vaccine was not significantly more protective against influenza-related hospitalization than were the standard-dose vaccines.ConclusionsThe high-dose recombinant vaccine conferred more protection against PCR-confirmed influenza than an egg-based standard-dose vaccine among adults between the ages of 50 and 64 years. (Funded by Sanofi; ClinicalTrials.gov number, NCT03694392.)

Influenza in Pregnancy: Prevention and Treatment: ACOG Committee Statement No. 7.

Pregnant and postpartum individuals are at significantly higher risk of serious complications related to seasonal and pandemic influenza infections compared with nonpregnant people. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists (ACOG) recommend that all adults receive an annual influenza vaccine and that individuals who are or will be pregnant during influenza season receive an inactivated or recombinant influenza vaccine as soon as it is available. Although the influenza vaccine significantly lowers the risk of severe disease, it will not prevent all infections. Obstetrician-gynecologists and other obstetric health care professionals should consider both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for pregnant individuals who present with symptoms of respiratory illness. Antiviral treatment should not be delayed while awaiting respiratory infection test results, and a patient's vaccination status should not affect the decision to treat. Obstetrician-gynecologists and other obstetric care professionals can help reduce disparities in influenza vaccination rates as well as severe outcomes related to influenza infection by strongly recommending influenza vaccination to all patients.