Higher Hemagglutination Inhibition Titers Research Articles

The immunodominance of antigenic site Sb on the H1 influenza virus hemagglutinin increases with high immunoglobulin titers of the cohorts and with young age, but not sex

The head domain of the hemagglutinin of influenza viruses plays a dominant role in the antibody response due to the presence of immunodominant antigenic sites that are the main targets of host neutralizing antibodies. For the H1 hemagglutinin, five major antigenic sites defined as Sa, Sb, Ca1, Ca2, and Cb have been described. Although previous studies have focused on defining the hierarchy of the antigenic sites of the hemagglutinin in different human cohorts, it is still unclear if the immunodominance profile of the antigenic sites might change with the antibody levels of individuals or if other demographic factors (such as exposure history, sex, or age) could also influence the importance of the antigenic sites. The major antigenic sites of influenza viruses hemagglutinins are responsible for eliciting most of the hemagglutination inhibition antibodies in the host. To determine the antibody prevalence towards each major antigenic site, we evaluated the hemagglutination inhibition against a panel of mutant H1 viruses, each one lacking one of the “classic” antigenic sites. Our results showed that the individuals from the Stop Flu NYU cohort had an immunodominant response towards the sites Sb and Ca2 of H1 hemagglutinin. A simple logistic regression analysis of the immunodominance profiles and the hemagglutination inhibition titers displayed by each donor revealed that individuals with high hemagglutination inhibition titers against the wild-type influenza virus exhibited higher probabilities of displaying an immunodominance profile dominated by Sb, followed by Ca2 (Sb > Ca2 profile), while individuals with low hemagglutination inhibition titers presented a higher chance of displaying an immunodominance profile in which Sb and Ca2 presented the same level of immunodominance (Sb = Ca2 profile). Finally, while age exhibited an influence on the immunodominance of the antigenic sites, biological sex was not related to displaying a specific immunodominance profile.

Immunological profile of mice immunized with a polyvalent virosome-based influenza vaccine

BackgroundInfluenza A virus (IAV) causes respiratory disease in pigs and is a major concern for public health. Vaccination of pigs is the most successful measure to mitigate the impact of the disease in the herds. Influenza-based virosome is an effective immunomodulating carrier that replicates the natural antigen presentation pathway and has tolerability profile due to their purity and biocompatibility.MethodsThis study aimed to develop a polyvalent virosome influenza vaccine containing the hemagglutinin and neuraminidase proteins derived from the swine IAVs (swIAVs) H1N1, H1N2 and H3N2 subtypes, and to investigate its effectiveness in mice as a potential vaccine for swine. Mice were immunized with two vaccine doses (1 and 15 days), intramuscularly and intranasally. At 21 days and eight months later after the second vaccine dose, mice were euthanized. The humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with a polyvalent influenza virosomal vaccine were investigated.ResultsOnly intramuscular vaccination induced high hemagglutination inhibition (HI) titers. Seroconversion and seroprotection (> 4-fold rise in HI antibody titers, reaching a titer of ≥ 1:40) were achieved in 80% of mice (intramuscularly vaccinated group) at 21 days after booster immunization. Virus-neutralizing antibody titers against IAV were detected at 8 months after vaccination, indicating long-lasting immunity. Overall, mice immunized with the virosome displayed greater ability for B, effector-T and memory-T cells from the spleen to respond to H1N1, H1N2 and H3N2 antigens.ConclusionsAll findings showed an efficient immune response against IAVs in mice vaccinated with a polyvalent virosome-based influenza vaccine.

Protection efficacy of the H1 and H3 bivalent virus-like particle vaccine against swine influenza virus infection

Swine influenza (SI) is widely prevalent in pig herds worldwide, causing huge economic losses to the pig industry and public health risks. The traditional inactivated swine influenza virus (SIV) vaccines are produced in chicken embryos, and egg-adaptive substitutions that occur during production process can impact vaccine effectiveness. Thus, developing an SI vaccine that can decrease the dependence on chicken embryos with a high immunogenicity is urgently needed. In this study, the utility of insect cell-derived SIV H1 and H3 bivalent virus-like particle (VLP) vaccines containing HA and M1 proteins of Eurasian avian-like (EA) H1N1 SIV and recent human-like H3N2 SIV were assessed in piglets. Antibody levels were monitored, and the protection efficacy of the vaccine after viral challenge was evaluated and compared with the inactivated vaccine. Results show that piglets produced high hemagglutination inhibition (HI) titers of antibodies against H1 and H3 SIV after immunization with SIV VLP vaccine. The neutralizing antibody level was significantly higher in SIV VLP vaccine than in the inactivated vaccine at 6 weeks post vaccination (p < 0.05). Furthermore, piglets immunized with the SIV VLP vaccine were protected against the challenge of H1 and H3 SIV, displaying inhibition of viral replication in piglets, and reduced lung damage. These results show that SIV VLP vaccine has good application prospects, thus laying the foundation for further research and commercialization of SIV VLP vaccine.

High prevalence of IgE sensitization to inactivated influenza vaccines, yet robust IgG4 responses, in a healthy pediatric population.

Anaphylaxis following influenza vaccination is a rare but serious problem. The underlying immune responses are not well understood. This study elucidated the IgE and IgG antibody responses in healthy children and adolescents following inactivated influenza vaccines (IIVs). The efficacy and safety of quadrivalent IIV (QIV) and trivalent IIV (TIV) were compared in healthy subjects aged 0-18 years. Serum IIV-specific IgE, IgG, and IgG4 levels (sIgE, sIgG, and sIgG4) were measured with ImmunoCAP. Hemagglutination inhibition (HI) assay was performed for each influenza virus subtype. Sera from earlier patients who developed anaphylaxis to different IIVs were similarly tested. A total of 393 subjects were enrolled: 96 were 6months-2years old, 100 were 3-5years old, 100 were 6-12 years old, and 97 were 13-18 years old. No anaphylaxis was observed. Generally, QIV and TIV induced similar antibody responses. IIV-sIgE levels rose significantly after vaccination in the 6months-2 years old and 3-5 years old groups, did not change in the 6-12 years old group, and decreased in the 13-18 years old group. In contrast, the IIV-sIgG4/sIgE ratio increased significantly after vaccination in all age groups. Sensitized subjects had significantly higher HI titers and IIV-sIgG levels in the youngest age group and higher IIV-sIgG4 levels in all age groups compared with the non-sensitized. The IIV-sIgG4/sIgE ratio in five patients with anaphylaxis was significantly lower than in age-matched healthy subjects. IIVs induce IgE sensitization in healthy children but also robust IgG4 responses that may protect them from anaphylaxis.

Low quality antibody responses in critically ill patients hospitalized with pandemic influenza A(H1N1)pdm09 virus infection

Although some adults infected with influenza 2009 A(H1N1)pdm09 viruses mounted high hemagglutination inhibition (HAI) antibody response, they still suffered from severe disease, or even death. Here, we analyzed antibody profiles in patients (n = 31, 17–65 years) admitted to intensive care units (ICUs) with lung failure and invasive mechanical ventilation use due to infection with A(H1N1)pdm09 viruses during 2009–2011. We performed a comprehensive analysis of the quality and quantity of antibody responses using HAI, virus neutralization, biolayer interferometry, enzyme-linked-lectin and enzyme-linked immunosorbent assays. At time of the ICU admission, 45% (14/31) of the patients had HAI antibody titers ≥ 80 in the first serum (S1), most (13/14) exhibited narrowly-focused HAI and/or anti-HA-head binding antibodies targeting single epitopes in or around the receptor binding site. In contrast, 42% (13/31) of the patients with HAI titers ≤ 10 in S1 had non-neutralizing anti-HA-stem antibodies against A(H1N1)pdm09 viruses. Only 19% (6/31) of the patients showed HA-specific IgG1-dominant antibody responses. Three of 5 fatal patients possessed highly focused cross-type HAI antibodies targeting the (K130 + Q223)-epitopes with extremely low avidity. Our findings suggest that narrowly-focused low-quality antibody responses targeting specific HA-epitopes may have contributed to severe infection of the lower respiratory tract.

A Novel Neuraminidase Virus-Like Particle Vaccine Offers Protection Against Heterologous H3N2 Influenza Virus Infection in the Porcine Model.

Influenza A viruses (IAVs) pose a global health threat, contributing to hundreds of thousands of deaths and millions of hospitalizations annually. The two major surface glycoproteins of IAVs, hemagglutinin (HA) and neuraminidase (NA), are important antigens in eliciting neutralizing antibodies and protection against disease. However, NA is generally ignored in the formulation and development of influenza vaccines. In this study, we evaluate the immunogenicity and efficacy against challenge of a novel NA virus-like particles (VLPs) vaccine in the porcine model. We developed an NA2 VLP vaccine containing the NA protein from A/Perth/16/2009 (H3N2) and the matrix 1 (M1) protein from A/MI/73/2015, formulated with a water-in-oil-in-water adjuvant. Responses to NA2 VLPs were compared to a commercial adjuvanted quadrivalent whole inactivated virus (QWIV) swine IAV vaccine. Animals were prime boost vaccinated 21 days apart and challenged four weeks later with an H3N2 swine IAV field isolate, A/swine/NC/KH1552516/2016. Pigs vaccinated with the commercial QWIV vaccine demonstrated high hemagglutination inhibition (HAI) titers but very weak anti-NA antibody titers and subsequently undetectable NA inhibition (NAI) titers. Conversely, NA2 VLP vaccinated pigs demonstrated undetectable HAI titers but high anti-NA antibody titers and NAI titers. Post-challenge, NA2 VLPs and the commercial QWIV vaccine showed similar reductions in virus replication, pulmonary neutrophilic infiltration, and lung inflammation compared to unvaccinated controls. These data suggest that anti-NA immunity following NA2 VLP vaccination offers comparable protection to QWIV swine IAV vaccines inducing primarily anti-HA responses.

Alternating 3 different influenza vaccines for swine in Europe for a broader antibody response and protection

Heterologous prime-boost vaccination with experimental or commercial influenza vaccines has been successful in various animal species. In this study, we have examined the efficacy of alternating 3 different European commercial swine influenza A virus (swIAV) vaccines: the trivalent Respiporc® FLU3 (TIV), the bivalent GRIPORK® (BIV) and the monovalent Respiporc® FLUpan H1N1 (MOV). Five groups of 6 pigs each received 3 vaccinations at 4–6 week intervals in a homologous or heterologous prime-boost regimen. A sixth group served as a mock-vaccinated challenge control. Four weeks after the last vaccination, pigs were challenged intranasally with a European avian-like H1N1 (1C.2.1) swIAV, which was antigenically distinct from the vaccine strains. One heterologous prime-boost group (TIV–BIV–MOV) had higher hemagglutination inhibition (HI) and neuraminidase inhibition antibody responses against a panel of antigenically distinct H1N1, H1N2 and H3N2 IAVs than the other heterologous prime-boost group (BIV–TIV–MOV) and the homologous prime-boost groups (3xTIV; 3xBIV; 3xMOV). Group TIV–BIV–MOV had seroprotective HI titers (≥ 40) against 56% of the tested viruses compared to 33% in group BIV–TIV–MOV and 22–39% in the homologous prime-boost groups. Post-challenge, group TIV–BIV–MOV was the single group with significantly reduced virus titers in all respiratory samples compared to the challenge control group. Our results suggest that the use of different commercial swIAV vaccines for successive vaccinations may result in broader antibody responses and protection than the traditional, homologous prime-boost vaccination regimens. In addition, the order in which the different vaccines are administered seems to affect the breadth of the antibody response and protection.

A novel digital device-based adjuvant-like effect for influenza vaccine: A feasibility and pilot study

Abstract Viral infections such as influenza and COVID-19 have a huge impact on humans. Previous studies showed that some exercise could enhance the anti-viral antibody titers after vaccination. We developed a novel digital device designed to enhance host immune system against viral infection by acting like adjuvants. The digital device, SAT-008, is a mobile application based on an algorithm to regulate physical activity. To assess the feasibility of SAT-008, a randomized, open-label, and controlled study was conducted for 13 weeks (Oct 20 to Jan 21). A total of 42 healthy adults (mostly healthcare workers) aged 24 to 46 years were recruited and finally 32 subjects served for analysis. A single-dose of quadrivalent inactivated influenza vaccine was administered for each subject. The control group maintained daily life without using SAT-008, while the experimental group (Exp) used SAT-008 during the study. As a result, compared to the controls, the Exp showed a significant increase in hemagglutination-inhibition (HI) titers of antigen subtype B Yamagata lineage after 4 weeks of vaccination and antigen subtype B Victoria lineage after 12 weeks of vaccination (P &amp;lt; 0.05), whereas the controls did not. As for type A influenza, there was no significant difference in HI titers between groups. In addition, the Exp was divided into high performers (HP) and low performers (LP) based on the adherence rate. The HP showed significantly higher HI titers of B Yamagata lineage in 12 weeks after vaccination than controls and LP (P &amp;lt; 0.05) and of B Victoria lineage than controls (P &amp;lt; 0.01). Our findings indicate a novel approach using digital device may play an important role to enhance host immune system to act as a vaccine adjuvant against viral diseases such as influenza. Supported by grants from S-Alpha Therapeutics, Inc.

Polyethyleneimine modified Pickering emulsion as a novel adjuvant to induce strong and long-lasting immune responses

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are widely-investigated vaccine adjuvants owing to their safety, antigen slow-release ability, and good adjuvants activity. This study involved the preparation of the polyethyleneimine-modified immunopotentiator Alhagi honey polysaccharide encapsulated PLGA nanoparticles (PEI-AHPP) and the assembly of the Pickering emulsion with PEI-AHPP as shell and squalene as core (PEI-PPAS). Furthermore, PEI-AHPP and PEI-PPAS were characterized. To assess the strength and type of immune responses induced by different adjuvants, the chickens were immunized with H9N2-absorbed nanoparticle formulations. Our results showed that since the PEI-PPAS possess rough strawberry-like surfaces, a large number of antigens can be absorbed on their surfaces through simple mixing. Compared to PEI-AHPP, PEI-PPAS was found to exhibit better stability and antigen-loading efficiency. The adjuvant activity of the nanoparticles showed PEI-PPAS/H9N2 to induce long-lasting and high Hemagglutination inhibition (HI) titers, high thymus, spleen, and organ index of the bursa of Fabricius. Moreover, the chickens immunized with PEI-PPAS/H9N2 showed a mixture of high CD4+ and CD8a+ T-cells in the spleen and strong Th1 and Th2-type cytokines secretion. Thus, these findings demonstrated PEI-PPAS to be a vaccine adjuvant inducing a mixed cellular and humoral immune response, which can potentially serve as an effective vaccine delivery adjuvant system for the H9N2 antigen.

Production of hyperimmune serum against genotype VII Newcastle disease virus in rabbits with several applications.

Objective:This study aimed to produce hyperimmune serum against genotype VII Newcastle disease virus (NDV) with several applications.Materials and Methods:Production of hyperimmune serum against genotype VII NDV was performed on eight New Zealand white rabbits divided into four groups. Rabbits were immunized three times on the 1st day, the 14th day, and the 30th day. Blood sampling was carried out on the 8th day after the third immunization.Results:All groups showed the same pattern of hemagglutination inhibition (HI) titer results. HI titers would peak on the 5th or the 9th day after the second immunization, then decrease until the 3rd day after the third immunization, and increase again on the 5th day after the third immunization. Rabbits immunized intravenously showed higher HI titers than the other groups. These results indicate that the intravenous route for hyperimmune serum production against genotype VII Newcastle disease virus greatly affects the immune response result.Conclusions:The production of hyperimmune serum by intravenous immunization three times was able to produce the highest titer of 210 at 38 days. The agar gel precipitation test and the Western blot assay showed that the hyperimmune serum was specific for the Newcastle disease antigen.

Ability to detect antibodies to beak and feather disease virus in blood on filter paper decreases with duration of storage.

BackgroundBeak and feather disease virus (BFDV) is a circovirus that infects captive and wild psittacine birds, and is of conservation concern. The haemagglutination inhibition (HI) assay is used to determine antibody titres against BFDV, and the use of dried blood spots (DBS) on filter paper stored at room temperature has been suggested to be an equally valid technique to the use of frozen serum. However, research on other pathogens has found variable results when investigating the longevity of antibodies stored on DBS at room temperature. Consequently, we aimed to test the temporal stability of antibodies to BFDV in DBS samples stored long-term at room temperature. A further goal was to add to the current knowledge of antibody response to naturally acquired BFDV infection in crimson rosellas (Platycercus elegans).MethodsBlood was collected from wild P. elegans in Victoria, Australia, that had been live-trapped (n = 9) or necropsied (n = 11). BFDV virus load data were obtained from blood stored in ethanol by real-time quantitative PCR (qPCR); antibody titres were obtained by HI assay from either DBS or serum samples, which had been collected concurrently. All HI assays were performed commercially by the Veterinary Diagnostic Laboratory (VDL) in Charles Sturt University, Australia, who were blind to BFDV blood status.ResultsHI titres from DBS stored at room temperature declined significantly over time (~80 weeks). By contrast, frozen serum samples assayed after 80 weeks in storage all had high HI titres, only varying up to one dilution step from the initial HI titres obtained from DBS at 3–6 weeks after sampling. Weak HI titres from DBS samples all came back negative when the test was repeated only nine weeks later. Novel high HI titres were reported in P. elegans, and while most birds with high antibody titres had corresponding negative qPCR results, a single subadult presented with high HI titres and virus load simultaneously.ConclusionDetection of antibodies on filter paper stored at room temperature decreases over time, increasing the chances of false negatives in these samples, and in repeated testing of samples with weak HI titres. Consequently, serum should be the preferred sample type to use for seroepidemiological studies on BFDV in parrots and other bird species. When not possible, it may help to store DBS on filter paper at −20 °C or lower. However, prompt testing of DBS samples (e.g., <6 weeks in storage) is recommended pending further research on antibody temporal stability. We also show that P. elegans, especially adults, can produce high antibody titres against BFDV, which may help them resist infection.

Inflammasome Activity in Response to Influenza Vaccination Is Maintained in Monocyte-Derived Peripheral Blood Macrophages in Older Adults.

Introduction: Each year, a disproportionate number of the total seasonal influenza-related hospitalizations (90%) and deaths (70%) occur among adults who are >65 years old. Inflammasome activation has been shown to be important for protection against influenza infection in animal models but has not yet been demonstrated in humans. We hypothesized that age-related dysfunction (immunosenescence) of the inflammasome may be associated with poor influenza-vaccine response among older adults. Methods: A cohort of younger (18–40 years of age) and older (≥65 years of age) adults was recruited prior to the 2014–2015 influenza season. We measured hemagglutination inhibition (HAI) titers in serum before and 28 days after receipt of the seasonal inactivated influenza vaccine. Inflammasome-related gene expression and protein secretion were quantified in monocyte-derived macrophages following stimulation with influenza A/H1N1 virus. Results: Younger adults exhibited higher HAI titers compared to older adults following vaccination, although inflammasome-related protein secretion in response to influenza stimulation was similar between the age groups. Expression of P2RX7 following influenza stimulation was lower among older adults. Interestingly, CFLAR expression was significantly higher among females (p = 2.42 × 10−5) following influenza stimulation and this gene may play an important role in the development of higher HAI antibody titers among older females. Conclusion: Inflammasome activation in response to influenza vaccination appears to be maintained in monocyte-derived macrophages from older adults and does not explain the poor influenza vaccine responses generally observed among this age group.

Accelerated Evolution of H7N9 Subtype Influenza Virus under Vaccination Pressure.

No avian H7N9 outbreaks have occurred since the introduction of H7N9 inactivated vaccine in the fall of 2017. However, H7N9 is still prevalent in poultry. To surveil the prevalence, genetic characteristics, and antigenic changes of H7N9, over 7000 oropharyngeal and cloaca swab specimens were collected from live poultry markets and farms in 15 provinces of China from 2017 to 2019. A total of 85 influenza virus subtype H7N9 strains were isolated and 20 representative strains were selected for genetic analysis and antigenicity evaluation. Results indicated the decreased prevalence of low-pathogenic H7N9 strains while highly-pathogenic H7N9 strains became dominated since the introduction of vaccine. Phylogenetic analysis showed that strains from 2019 formed an independent small branch and were genetically distant to strains isolated in 2013–2018. Analysis of key amino acid sites showed that the virus strains may adapt to the host environment evolutionally through mutation. Our analysis predicted additional potential glycosylation sites for HA and NA genes in the 2019 strains. Sequence analysis of HA gene in strains isolated from 2018 to 2019 showed that there were an increased nucleotide substitution rate and an increased mutation rate in the first and second nucleotides of coding codons within the open reading frame. The hemagglutination inhibition (HI) assay showed that H7-Re1 and H7-Re2 exhibited a lower HI titer for isolates from 2019, while H7-Re3 and rLN79 showed a high HI titer. The protective effect of the vaccine decreased after 15 months of use. Overall, under vaccination pressure, the evolution of influenza virus subtype H7N9 has accelerated.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12250-021-00383-x.

Growth properties and immunogenicity of a virus generated by reverse genetics for an inactivated equine influenza vaccine.

Keeping vaccine strains up to date is the key to controlling equine influenza (EI). Viruses generated by reverse genetics (RG) are likely to be effective for quickly updating a vaccine strain. To evaluate the growth properties of an RG virus in embryonated chicken eggs, and to evaluate antibody responses to a formalin-inactivated vaccine derived from the RG virus in Thoroughbred horses. In vitro and in vivo experiments. Wild-type (WT) viruses (A/equine/Ibaraki/1/2007) or RG viruses (consisting of haemagglutinin [HA] and neuraminidase genes derived from A/equine/Ibaraki/1/2007 and the six other genes derived from high-growth A/Puerto Rico/8/34) were inoculated into embryonated chicken eggs, and the allantoic fluids were harvested at every 24 hours after inoculation. WT and RG viruses were inactivated by formalin for vaccine use. Ten unvaccinated yearlings (five each for WT or RG vaccine) received the first two doses of a primary vaccination course 4 weeks apart followed by their third dose 12 weeks later. Twenty vaccinated adult horses (10 each for WT or RG vaccine) received a single dose of a booster vaccination. The RG virus had high growth properties in embryonated chicken eggs. Unvaccinated yearlings responded poorly to the first vaccination, especially those that received the RG vaccine, but mounted better responses to the second and the third vaccinations, and maintained relatively high haemagglutination inhibition (HI) titres up to 28 weeks after the first vaccination. Vaccinated adult horses did not respond remarkably to the booster vaccination, but no horses showed titres below their pre-booster values even at 12 weeks after vaccination. The RG virus elicited immunogenicity in horses adequate for vaccine use. No virus challenge study was performed. The RG viruses are useful as an EI vaccine strain, and quick updates of an EI vaccine strain can be achieved by using RG techniques.

Probiotic Lactobacilli Enhance Immunogenicity of an Inactivated H9N2 Influenza Virus Vaccine in Chickens.

Avian influenza viruses (AIVs) infect a wide range of hosts, including humans and many avian species. Efforts have been made to control this pathogen in chickens using vaccination programs, but that has been met with varying degrees of success. Therefore, identification of more efficacious vaccination strategies is warranted. This study was undertaken to investigate the potential effects of probiotics on the immunogenicity of a beta-propiolactone-whole inactivated virus (WIV) vaccine of H9N2 subtype adjuvanted with the Toll-like receptor-21 ligand, CpG oligodeoxynucleotides 2007 (CpG). Eighty-four 1-day-old White Leghorn layers were allocated into six groups. Two out of six groups received a mixture of probiotic Lactobacillus spp. (PROB) biweekly from days 1 35 of age. Chickens were intramuscularly vaccinated with WIV either alone or adjuvanted with AddaVax™ (WIV+Add) or CpG (WIV+CpG), and one group received saline (phosphate-buffered saline). Primary and secondary vaccinations occurred at days 14 and 28 of age, respectively. The results revealed that the group that received probiotics and was vaccinated with CpG-adjuvanted WIV H9N2 vaccine had higher hemagglutination inhibition titers than the other treatment groups at days 14 and 21 postprimary vaccination. Probiotics did not induce higher IgM or IgY titers in chickens receiving the WIV vaccine only. Concerning their effect on cell-mediated immune responses, probiotics enhanced interferon-gamma (IFN-γ) gene expression and significantly increased secretion of IFN-γ protein by splenocytes in chickens vaccinated with CpG-adjuvanted WIV H9N2. Together, these findings suggest the use of probiotics to enhance the immunogenicity of CpG-adjuvanted WIV H9N2 vaccines. Additional studies are required to better understand the specific interactions between probiotics and the gut microbiota and different types of cells of the gastrointestinal tract to decipher the underlying mechanisms of how probiotics modulate immune responses to vaccines.

The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination.

(1) Background: The influenza virus continues to cause significant annual morbidity and mortality. The overall efficacy of seasonal influenza vaccination is suboptimal, which is partly due to host immune factors. The effects of imprinting and repeated seasonal influenza vaccination were investigated to assess for immune factors and mechanisms that impact influenza vaccine responses. (2) Methods: Twenty participants were enrolled into a prospective pilot study based on birth cohort and seasonal influenza immunization history. Immunologic parameters were assessed over a six-month period after the seasonal influenza vaccine was administered. (3) Results: There was no significant imprinting effect, as measured by hemagglutination inhibition (HAI) fold change, HAI geometric mean titer (GMT) for Day 29 or Day 180 post-vaccination and antigen- specific antibody-secreting cells (ASC) for Day 8 post-vaccination. Individuals who had minimal prior seasonal influenza vaccination had a higher magnitude ASC response and a higher HAI fold change post-vaccination than individuals who were repeatedly vaccinated. (4) Conclusions: Repeated seasonal influenza vaccination resulted in a decreased fold change of the immune response, although individuals in this cohort tended to have high HAI titers at baseline that persisted after vaccination. Imprinting effects were not observed in this cohort. These host immune factors should be considered in the development of universal influenza vaccines. ClinicalTrials.gov Identifier: NCT03686514.

Molecular and biological characterization of the immunological potency of Newcastle disease virus oil emulsion-inactivated vaccines prepared from field isolate obtained from vaccinated chickens outbreak.

This study was conducted to characterize the immunological parameters of chickens vaccinated with two formulated inactivated vaccines, water in oil (WO) and water in oil in water (WOW), prepared from velogenic Newcastle disease virus (vNDV) genotype VIIj isolated from outbreak among vaccinated chickens. Six groups (G1-G6) of commercial broiler chickens were established (n = 20). The G1-G3 were received homologous (WO and WOW) and heterologous (LaSota) inactivated vaccines, respectively. The G4 was vaccinated with live heterologous (LaSota) vaccine, while G5 and G6 were kept as control positive and control negative non-vaccinated groups. The antibody titers were measured against vNDV and LaSota antigens using hemagglutination inhibition (HI) test, the cytokine gene expressions of IFNγ, IL1β, IL4, IL6, IL8, and IL18 were quantified using real-time RT-PCR, and the virus shedding was titrated on chicken embryo fibroblast cells after challenging by vNDV. The classical clinical signs and 100% mortality were observed only in G5 after vNDV challenging. The highest HI titers were detected in G1, G2, and G3 using NDV/168 antigen with no significant differences among them. These groups showed higher HI titer than G4 (2-4log2). Cytokine gene expression of IFNγ, IL1, IL6, IL8, and IL18 were significantly downregulated in vaccinated chickens with upregulation of IL4 than non-vaccinated challenge group. Viral shedding titers were significantly (0.0001, p ≤ 0.001) reduced in all samples form vaccinated chickens. In conclusion, the prepared vaccines produced highly efficient immunological responses and could be used for controlling the NDV infection.

Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination.

Maximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to explain study discrepancies and to provide guidance for the future use of vitamin supplements at the time of vaccination. We conducted a randomized, blinded, placebo-controlled study of influenza virus vaccination and vitamin supplementation among 2 to 8 (inclusive) year old children over three seasons, including 2015–2016 (n = 9), 2016–2017 (n = 44), and 2017–2018 (n = 26). Baseline measurements of vitamins A and D were obtained from all participants. Measurements were of serum retinol, retinol-binding protein (RBP, a surrogate for retinol), and 25-hydroxyvitamin D (25(OH)D). Participants were stratified into two groups based on high and low incoming levels of RBP. Children received two doses of the seasonal influenza virus vaccine on days 0 and 28, either with an oral vitamin supplement (termed A&D; 20,000 IU retinyl palmitate and 2000 IU cholecalciferol) or a matched placebo. Hemagglutination inhibition (HAI) antibody responses were evaluated toward all four components of the influenza virus vaccines on days 0, 28, and 56. Our primary data were from season 2016–2017, as enrollment was highest in this season and all children exhibited homogeneous and negative HAI responses toward the Phuket vaccine at study entry. Responses among children who entered the study with insufficient or deficient levels of RBP and 25(OH)D benefited from the A&D supplement (p < 0.001 for the day 28 Phuket response), whereas responses among children with replete levels of RBP and 25(OH)D at baseline were unaffected or weakened (p = 0.02 for the day 28 Phuket response). High baseline RBP levels associated with high HAI titers, particularly for children in the placebo group (baseline RBP correlated positively with Phuket HAI titers on day 28, r = 0.6, p = 0.003). In contrast, high baseline 25(OH)D levels associated with weak HAI titers, particularly for children in the A&D group (baseline 25(OH)D correlated negatively with Phuket HAI titers on day 28, r = −0.5, p = 0.02). Overall, our study demonstrates that vitamin A&D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at baseline. Results provide guidance for the appropriate use of vitamins A and D in future clinical vaccine studies.

Optimal timing of influenza vaccine during pregnancy: A systematic review and meta-analysis.

BackgroundPregnant women have an elevated risk of illness and hospitalisation from influenza. Pregnant women are recommended to be prioritised for influenza vaccination during any stage of pregnancy. The risk of seasonal influenza varies substantially throughout the year in temperate climates; however, there is limited knowledge of how vaccination timing during pregnancy impacts the benefits received by the mother and foetus.ObjectivesTo compare antenatal vaccination timing with regard to influenza vaccine immunogenicity during pregnancy and transplacental transfer to their newborns.MethodsStudies were eligible for inclusion if immunogenicity to influenza vaccine was evaluated in women stratified by trimester of pregnancy. Haemagglutination inhibition (HI) titres, stratified by trimester of vaccination, had to be measured at either pre‐vaccination and within one month post‐vaccination, post‐vaccination and at delivery in the mother, or in cord/newborn blood. Authors searched PubMed, Scopus, Web of Science and EMBASE databases from inception until June 2016 and authors of identified studies were contacted for additional data. Extracted data were tabulated and summarised via random‐effect meta‐analyses and qualitative methods.ResultsSixteen studies met the inclusion criteria. Meta‐analyses found that compared with women vaccinated in an earlier trimester, those vaccinated in a later trimester had a greater fold increase in HI titres (1.33‐ to 1.96‐fold) and higher HI titres in cord/newborn blood (1.21‐ to 1.64‐fold).ConclusionsThis review provides comparative analysis of the effect of vaccination timing on maternal immunogenicity and protection of the infant that is informative and relevant to current vaccine scheduling for pregnant women.

The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients-a 6-month follow-up prospective study.

Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as theymight exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications. The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response. One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3-5weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3-5weeks. Sera were collected before vaccination, 18-90days after each vaccination, and more than 180days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA. Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HIGMT and seroprotection was observed only in AIRD at > 180days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future. Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRDis needed.