Immune Interference Research Articles

Local and systemic humoral immune responses to Histophilus somni recombinant antigens administered intranasally and subcutaneously to dairy calves

Bovine respiratory disease (BRD) causes significant economic losses in dairy calves. Induction of an early immune response via parenteral vaccination is complicated by the interference of colostral immunity. In this study, we investigated early immunization against selected conserved bacterial antigens. Calves were vaccinated twice intranasally and then subcutaneously with Histophilus somni recombinant proteins (rOMP40 or rHsp60) mixed with one of two adjuvants: CpG ODN2007 or MPLA. The control group (Con) was treated with PBS. The first immunization was done between 24 and 48 h of life and then twice in two weeks intervals. Blood, nasal, and saliva secretion samples were collected directly before vaccination (S1–S3) and then on 42–44 (S4) and 59–61 (S5) day of life. Antibodies (IgG1/IgG2/IgM/IgA in serum; IgG1/IgA in secretions) against both vaccine antigens were quantified in all samples. Intranasal and subcutaneous vaccinations using the described formulas did not increase antibody reactivity against the tested proteins. The reactivity of serum IgG1, IgM, and IgA anti-rOMP40 antibodies was significantly higher in S1 in all groups than that in the other samplings (p˂0.01). Significant differences in the reactivity of serum anti-rOMP40 antibodies between groups were identified in S1 (IgA reactivity was higher in the CpG vs. MPLA group; p < 0.05), S4 (IgM reactivity was higher in Con vs. CpG group; p < 0.05), and S5 (IgG1 reactivity was higher in MPLA vs. Con group; p < 0.05). The lack of consistent changes in antibodies after immunization (S4 and S5) hinders the drawing of conclusions regarding the effect of immunization on antibody reactivity. In the future, establishing a proper immunization window and adjuvants for nasal vaccines against bacterial pathogens causing BRD in calves remains to be determined.

A pentavalent peptide vaccine elicits Aβ and tau antibodies with prophylactic activity in an Alzheimer’s disease mouse model

Amyloid-β (Aβ) and hyperphosphorylated tau protein are targets for Alzheimer’s Disease (AD) immunotherapies, which are generally focused on single epitopes within Aβ or tau. However, due to the complexity of both Aβ and tau in AD pathogenesis, a multipronged approach simultaneously targeting multiple epitopes of both proteins could overcome limitations of monotherapies. Herein, we propose an active AD immunotherapy based on a nanoparticle vaccine comprising two Aβ peptides (1–14 and pyroglutamate pE3-14) and three tau peptides (centered on phosphorylated pT181, pT217 and pS396/404). These correspond to both soluble and aggregated targets and are displayed on the surface of immunogenic liposomes in an orientation that maintains reactivity with epitope-specific monoclonal antibodies. Intramuscular immunization of mice with individual epitopes resulted in minimally cross-reactive antibody induction, while simultaneous co-display of 5 antigens (“5-plex”) induced antibodies against all epitopes without immune interference. Post-immune sera recognized plaques and neurofibrillary tangles from human AD brain tissue. Vaccine administration to 3xTg-AD mice using a prophylactic dosing schedule inhibited tau and amyloid pathologies and resulted in improved cognitive function. Immunization was well tolerated and did not induce antigen-specific cellular responses or persistent inflammatory responses in the peripheral or central nervous system. Antibody levels could be reversed by halting monthly vaccinations. Altogether, these results indicate that active immune therapies based on nanoparticle formulations of multiple Aβ and tau epitopes warrant further study for treating early-stage AD.

A robust high-throughput functional screening assay for plant pathogen effectors using the TMV-GFP vector.

Uncovering the function of phytopathogen effectors is crucial for understanding mechanisms of pathogen pathogenicity and for improving our ability to protect plants from diseases. An increasing number of effectors have been predicted in various plant pathogens. Functional characterization of these effectors has become a major focus in the study of plant-pathogen interactions. In this study, we designed a novel screening system that combines the TMV (tobacco mosaic virus)-GFP vector and Agrobacterium-mediated transient expression in the model plant Nicotiana benthamiana. This system enables the rapid identification of effectors that interfere with plant immunity. The biological function of these effectors can be easily evaluated by observing the GFP fluorescence signal using a UV lamp within just a few days. To evaluate the TMV-GFP system, we initially tested it with well-described virulence and avirulence type III effectors from the bacterial pathogen Ralstonia solanacearum. After proving the accuracy and efficiency of the TMV-GFP system, we successfully screened a novel virulence effector, RipS1, using this approach. Furthermore, using the TMV-GFP system, we reproduced consistent results with previously known cytoplasmic effectors from a diverse array of pathogens. Additionally, we demonstrated the effectiveness of the TMV-GFP system in identifying apoplastic effectors. The easy operation, time-saving nature, broad effectiveness, and low technical requirements of the TMV-GFP system make it a promising approach for high-throughput screening of effectors with immune interference activity from various pathogens.

Immunogenicity and safety of concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine in Chinese adults: An open-label, randomized, controlled trial

ABSTRACT The immunogenicity and safety of the concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine (Split Virion) (QIIV) in Chinese adults are unclear. In this open-label, randomized controlled trial, participants aged ≥ 18 years were recruited. Eligible healthy adults were randomly assigned (1:1) to receive QIIV at the same time as the first dose of COVID-19 vaccine (simultaneous-group) or 14 days after the second dose of COVID-19 vaccine (non-simultaneous-group). The primary outcome was to compare the difference in immunogenicity of QIIV (H1N1, H3N2, Yamagata, and Victoria) between the two groups. A total of 299 participants were enrolled, 149 in the simultaneous-group and 150 in the non-simultaneous-group. There were no significant differences in geometric mean titer (GMT) [H1N1: 386.4 (95%CI: 299.2–499.0) vs. 497.4 (95%CI: 377.5–655.3); H3N2: 66.9 (95%CI: 56.1–79.8) vs. 81.4 (95%CI: 67.9–97.5); Yamagata: 95.6 (95%CI: 79.0–115.8) vs. 74.3 (95%CI: 58.6–94.0); and Victoria: 48.5 (95%CI: 37.6–62.6) vs. 65.8 (95%CI: 49.0–88.4)] and seroconversion rate (H1N1: 87.5% vs. 90.1%; H3N2: 58.1% vs. 62.0%; Yamagata: 75.0% vs. 64.5%; and Victoria: 55.1% vs. 62.8%) of QIIV antibodies between the simultaneous and non-simultaneous groups. For the seroprotection rate of QIIV antibodies, a higher seroprotection rate of Yamagata antibody was observed only in the simultaneous-group than in the non-simultaneous-group [86.0% vs. 76.0%, p = .040]. In addition, no significant difference in adverse events was observed between the two groups (14.2% vs. 23.5%, p = .053). In conclusion, no immune interference or safety concerns were found for concomitant administration of COVID-19 vaccine with QIIV in adults aged ≥ 18 years.

Immune interface interference vaccines: An evolution-informed approach to anti-bacterial vaccine design.

Developing protein-based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti-bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high-throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, 'immune interface interference' (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H-binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein-based vaccines to prevent bacterial infections.

Assessment of the immune interference effects of multivalent vaccine for influenza epidemic strain in 2022–2023 and evaluation of its efficacy

The various strains of influenza virus cause respiratory symptoms in humans every year and annual vaccinations are recommended. Due to its RNA-type genes and segmented state, it belongs to a virus that mutates frequently with antigenic drift and shift, giving rise to various strains. Each year, the World Health Organization identifies the epidemic strains and operates a global surveillance system to suggest the viral composition for the influenza vaccine. Influenza viruses, which have multiple viral strains, are produced in the format of multivalent vaccine. However, the multivalent vaccine has a possibility of causing immune interference by introducing multiple strain-specific antigens in a single injection. Therefore, evaluating immune interference phenomena is essential when assessing multivalent vaccines. In this study, the protective ability and immunogenicity of multivalent and monovalent vaccines were evaluated in mice to assess immune interference in the multivalent vaccine. Monovalent and multivalent vaccines were manufactured using the latest strain of the 2022–2023 seasonal influenza virus selected by the World Health Organization. The protective abilities of both types of vaccines were tested through hemagglutination inhibition test. The immunogenicity of multivalent and monovalent vaccines were tested through enzyme-linked immunosorbent assay to measure the cellular and humoral immunity expression rates. As a result of the protective ability and immunogenicity test, higher level of virus neutralizing ability and greater amount of antibodies in both IgG1 and IgG2 were confirmed in the multivalent vaccine. No immune interference was found to affect the protective capacity and immune responses of the multivalent vaccines.

Rapid Decline of SARS-CoV-2 Viral Load in Single vs. Double-Dose (Short-Interval

The present work was carried out during the emergence of Delta Variant of Concern (VoC) and aimed to study the change in SARS CoV-2 viral load in Covishield vaccinated asymptomatic/mildly symptomatic health-care workers (HCWs) to find out the optimum isolation period. The SARS CoV-2 viral load was carried out in sequential samples of 55 eligible HCWs which included unvaccinated (UnV; n = 11), single-dose vaccinated (SDV, n = 20) and double-dose vaccinated [DDV, n = 24; short-interval (<6weeks)] subjects. The mean load of envelope (E) gene on day 5 in SDV [0.42 × 105 copies/reaction] was significantly lower as compared to DDV [6.3 × 105 copies/reaction, P = 0.005] and UnV [6.6 × 105 copies/reaction, P = 0.001] groups. The rate of decline of SARS CoV-2 viral load in the initial 5days of PCR positivity was significantly higher in SDV as compared to that in DDV (Mean log decline 0.39 vs. 0.19; P < 0.001). This was possibly due to interference of adenoviral immunity of first dose of adenovirus-vectored vaccine in double-dose vaccinated HCWs who had received vaccines within a shorter interval (<6weeks).

Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: implications of immune imprinting and interference

ObjectivesConcomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination. MethodsAn open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay. ResultsGroup C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of −2.6% [95% CI, −18 to 13.4]; 44.2% vs. 57.1%, difference of −13.0% [95% CI to −28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups. DiscussionConcomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains.

Subcellular Colocalization Assay of Host Factors with Viral Replication Complex in the dsRNA Reporter Nicotiana benthamiana.

As obligate pathogens, plant viruses co-opt several host factors for viral replication. Double-stranded RNA (dsRNA) plays important roles in plants, including eliciting innate immune responses and RNA interference. dsRNA also represents the genetic entities of a number of viruses and is a marker of infection by positive-sense single-stranded RNA viruses. Previous detection methods for RNA viruses basically relied on immunological methods, but later researchers discovered that the dsRNA-binding domain of the Flock house virus B2 protein is a perfect alternative to the J2 mAb for sensitive and rapid detection of long dsRNA in vitro and in vivo, and developed B2:GFP transgenic Nicotiana benthamiana line. This method describes in detail how to visualize host factors in the viral replication complex in time and space with the help of B2:GFP transgenic plants, exemplified by Turnip mosaic virus (TuMV), a representative virus member of the Potyviruses.

Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines.

Glycoconjugate vaccines play a major role in the prevention of infectious diseases worldwide, with significant impact on global health, enabling the polysaccharides to induce immunogenicity in infants and immunological memory. Tetanus toxoid (TT), a chemically detoxified bacterial toxin, is among the few carrier proteins used in licensed glycoconjugate vaccines. The recombinant full-length 8MTT was engineered in E. coli with eight individual amino acid mutations to inactivate three toxin functions. Previous studies in mice showed that 8MTT elicits a strong IgG response, confers protection, and can be used as a carrier protein. Here, we compared 8MTT to traditional carrier proteins TT and cross-reactive material 197 (CRM197), using different polysaccharides as models: Group A Streptococcus cell-wall carbohydrate (GAC), Salmonella Typhi Vi, and Neisseria meningitidis serogroups A, C, W, and Y. The persistency of the antibodies induced, the ability of the glycoconjugates to elicit booster response after re-injection at a later time point, the eventual carrier-induced epitopic suppression, and immune interference in multicomponent formulations were also evaluated. Overall, immunogenicity responses obtained with 8MTT glycoconjugates were compared to those obtained with corresponding TT and, in some cases, were higher than those induced by CRM197 glycoconjugates. Our results support the use of 8MTT as a good alternative carrier protein for glycoconjugate vaccines, with advantages in terms of manufacturability compared to TT.

Mild traumatic brain injury in Drosophila melanogaster alters reactive oxygen and nitrogen species in a sex-dependent manner

Traumatic brain injury (TBI) is an outside force causing a modification in brain function and/or structural brain pathology that upregulates brain inducible nitric oxide synthase (iNOS), instigating increased levels of nitric oxide activity which is implicated in secondary pathology leading to behavioral deficits (Hall et al., 2012; Garry et al., 2015; Kozlov et al., 2017). In mammals, TBI-induced NO production activates an immune response and potentiates metabolic crisis through mitochondrial dysfunction coupled with vascular dysregulation; however, the direct influence on pathology is complicated by the activation of numerous secondary cascades and activation of other reactive oxygen species. Drosophila TBI models have demonstrated key features of mammalian TBI, including temporary incapacitation, disorientation, motor deficits, activation of innate immunity (inflammation), and autophagy responses observed immediately after injury (Katzenberger et al., 2013; Barekat et al., 2016; Simon et al., 2017; Anderson et al., 2018; Buhlman et al., 2021b). We hypothesized that acute behavioral phenotypes would be associated with deficits in climbing behavior and increased oxidative stress. Because flies lack mammalian-like cardiovascular and adaptive immune systems, we were able to make our observations in the absence of vascular disruption and adaptive immune system interference in a system where highly targeted interventions can be rapidly evaluated.To demonstrate the induction of injury, ten-day-old transgenic flies received an injury of increasing angles from a modified high impact trauma (HIT) device where angle-dependent increases occurred for acute neurological behavior assessments and twenty-four-hour mortality, and survival was significantly decreased. Injury caused sex-dependent effects on climbing activity and measures of oxidative stress. Specifically, after a single 60-degree HIT, female flies exhibited significant impairments in climbing activity beyond that observed in male flies. We also found that several measures of oxidative stress, including Drosophila NOS (dNOS) expression, protein nitration, and hydrogen peroxide production were significantly decreased in female flies. Interestingly, protein nitration was also decreased in males, but surpassed sham levels with a more severe injury. We also observed decreased autophagy demand in vulnerable dopaminergic neurons in female, but not male flies. In addition, mitophagy initiation was decreased in females.Collectively, our data suggest that TBI in flies induces acute behavioral phenotypes and climbing deficits that are analogous to mammalian TBI. We also observed that various indices of oxidative stress, including dNOS expression, protein tyrosine nitration, and hydrogen peroxide levels, as well as basal levels of autophagy, are altered in response to injury, an effect that is more pronounced in female flies.

Evaluating the benefit of serology during potential Australian bat lyssavirus and rabies post-exposure prophylaxis

Post-exposure prophylaxis (PEP) for potential lyssavirus exposures consists of wound management, rabies vaccination and may include rabies immunoglobulin (RIG). Rabies serology is sometimes indicated if there is risk of PEP failure. ObjectivesEvaluate the benefit of serology by indication. MethodsChart review of potential lyssavirus exposures managed at a Public Health Unit (June 2015 – December 2022) where serology was requested was conducted. The proportion of non-therapeutic titres was compared by sex, age, Indigenous status, serology indication, and whether RIG was given. Results46 notifications with serology were included. Males (5/19) and people over 40 (3/16) were more likely to demonstrate a non-therapeutic response. 2/3 of cases where vaccine doses were not given in the deltoid were non-therapeutic. The rate of non-therapeutic titres was similar for RIG given into the ipsilateral arm (2/11) and given excess RIG for weight (1/4). Although this small sample was inconclusive in isolation, it was also noted that all cases who did not receive RIG had therapeutic serology, whereas 6/35 of those receiving RIG had non-therapeutic serology. ConclusionsThis study supports broader literature questioning the utility of systemic RIG administration as likely limited and potentially detrimental considering the increased risk of immune interference. Implications for public healthHighlights a need to review Australian national guidelines to align with World Health Organization advice recommending local RIG administration only.

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules?

BackgroundIn 2019, the 3 + 1 schedule for children’s vaccination (2–4–6–18 months old) was changed for a reduced 2 + 1 schedule (2–4–12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. MethodsWe conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children’s blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. ResultsA total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65–0.90), 0.66 (0.55–0.79), 0.72 (0.52–0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. ConclusionInfant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children’s protection.

Development of a Novel Canine Parvovirus Vaccine Capable of Stimulating Protective Immunity in Four-Week-Old Puppies in the Face of High Levels of Maternal Antibodies.

Many highly effective vaccines have been developed to protect dogs against disease caused by canine parvovirus, but despite this vaccine interference by maternally derived antibodies continues to cause immunisation failure. To help overcome this limitation we have developed a novel, recombinant canine parvovirus type 2c vaccine strain, based on the structural and non-structural elements of an established type 2 vaccine. This novel CPV-2c vaccine strain has unique efficacy in the field, it is able to induce sterilising immunity in naïve animals 3 days after vaccination and is able to overcome very high levels of maternally derived antibodies from 4 weeks of age-thus closing the immunity gap to canine parvovirus infection in young puppies. The vaccine strain, named 630a, has been combined with an established canine distemper virus Onderstepoort vaccine strain to produce a new bivalent vaccine (Nobivac DP PLUS), intended to immunise very young puppies in the face of high levels of maternally derived antibody. Here, we describe the onset of immunity and maternal antibody interference studies that support the unique efficacy of the strain, and present overdose studies in both dogs and cats that demonstrate the vaccine to be safe.

Using model systems to unravel host-Pseudomonas aeruginosa interactions.

Using model systems in infection biology has led to the discoveries of many pathogen-encoded virulence factors and critical host immune factors to fight pathogenic infections. Studies of the remarkable Pseudomonas aeruginosa bacterium that infects and causes disease in hosts as divergent as humans and plants afford unique opportunities to shed new light on virulence strategies and host defence mechanisms. One of the rationales for using model systems as a discovery tool to characterise bacterial factors driving human infection outcomes is that many P. aeruginosa virulence factors are required for pathogenesis in diverse different hosts. On the other side, many host signalling components, such as the evolutionarily conserved mitogen-activated protein kinases, are involved in immune signalling in a diverse range of hosts. Some model organisms that have less complex immune systems also allow dissection of the direct impacts of innate immunity on host defence without the interference of adaptive immunity. In this review, we start with discussing the occurrence of P. aeruginosa in the environment and the ability of this bacterium to cause disease in various hosts as a natural opportunistic pathogen. We then summarise the use of some model systems to study host defence and P. aeruginosa virulence.

Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial.

Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and the quadrivalent influenza vaccine, and determined if concurrent administration would have effects on safety or immunogenicity. TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at the Radboud University Medical Centre, the Netherlands. Individuals ≥60 years, fully vaccinated against COVID-19 were eligible for participation and randomized into one of four study groups: 1) 0.5ml influenza vaccination Vaxigrip Tetra followed by 0.3ml BNT162b2 COVID-19 booster vaccination 21 days later, (2) COVID-19 booster vaccination followed by influenza vaccination, (3) influenza vaccination concurrent with the COVID-19 booster vaccination, and (4) COVID-19 booster vaccination only (reference group). Primary outcome was the geometric mean concentration (GMC) of IgG against the spike (S)-protein of the SARS-CoV-2 virus, 21 days after booster vaccination. We performed a non-inferiority analysis of concurrent administration compared to booster vaccines alone with a predefined non-inferiority margin of-0.3 on the log10-scale. 154 individuals participated from October, 4, 2021, until November, 5, 2021. Anti-S IgG GMCs for the co-administration and reference group were 1684 BAU/ml and 2435 BAU/ml, respectively. Concurrent vaccination did not meet the criteria for non-inferiority (estimate-0.1791, 95% CI -0.3680 to-0.009831) and antibodies showed significantly lower neutralization capacity compared to the reference group. Reported side-effects were mild and did not differ between study groups. Concurrent administration of both vaccines is safe, but the quantitative and functional antibody responses were marginally lower compared to booster vaccination alone. Lower protection against COVID-19 with concurrent administration of COVID-19 and influenza vaccination cannot be excluded, although additional larger studies would be required to confirm this. EudraCT: 2021-002186-17. The study was supported by the ZonMw COVID-19 Programme.

Seasonality influences key physiological components contributing to Culex pipiens vector competence.

Mosquitoes are the most important animal vector of disease on the planet, transmitting a variety of pathogens of both medical and veterinary importance. Mosquito-borne diseases display distinct seasonal patterns driven by both environmental and biological variables. However, an important, yet unexplored component of these patterns is the potential for seasonal influences on mosquito physiology that may ultimately influence vector competence. To address this question, we selected Culex pipiens, a primary vector of the West Nile virus (WNV) in the temperate United States, to examine the seasonal impacts on mosquito physiology by examining known immune and bacterial components implicated in mosquito arbovirus infection. Semi-field experiments were performed under spring, summer, and late-summer conditions, corresponding to historically low-, medium-, and high-intensity periods of WNV transmission, respectively. Through these experiments, we observed differences in the expression of immune genes and RNA interference (RNAi) pathway components, as well as changes in the distribution and abundance of Wolbachia in the mosquitoes across seasonal cohorts. Together, these findings support the conclusion that seasonal changes significantly influence mosquito physiology and components of the mosquito microbiome, suggesting that seasonality may impact mosquito susceptibility to pathogen infection, which could account for the temporal patterns in mosquito-borne disease transmission.

Immune interference in effectiveness of influenza and COVID-19 vaccination.

Vaccines are known to function as the most effective interventional therapeutics for controlling infectious diseases, including polio, smallpox, rabies, tuberculosis, influenza and SARS-CoV-2. Smallpox has been eliminated completely and polio is almost extinct because of vaccines. Rabies vaccines and Bacille Calmette-Guérin (BCG) vaccines could effectively protect humans against respective infections. However, both influenza vaccines and COVID-19 vaccines are unable to eliminate these two infectious diseases of their highly variable antigenic sites in viral proteins. Vaccine effectiveness (VE) could be negatively influenced (i.e., interfered with) by immune imprinting of previous infections or vaccinations, and repeated vaccinations could interfere with VE against infections due to mismatch between vaccine strains and endemic viral strains. Moreover, VE could also be interfered with when more than one kind of vaccine is administrated concomitantly (i.e., co-administrated), suggesting that the VE could be modulated by the vaccine-induced immunity. In this review, we revisit the evidence that support the interfered VE result from immune imprinting or repeated vaccinations in influenza and COVID-19 vaccine, and the interference in co-administration of these two types of vaccines is also discussed. Regarding the development of next-generation COVID-19 vaccines, the researchers should focus on the induction of cross-reactive T-cell responses and naive B-cell responses to overcome negative effects from the immune system itself. The strategy of co-administrating influenza and COVID-19 vaccine needs to be considered more carefully and more clinical data is needed to verify this strategy to be safe and immunogenic.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina

BackgroundIn yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration.MethodsWe conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests.ResultsOf 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted.ConclusionEffective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration.Trial RegistrationThe study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Immunogenicity and safety of the non-typable Haemophilus influenzae–Moraxella catarrhalis (NTHi-Mcat) vaccine administered following the recombinant zoster vaccine versus administration alone: Results from a randomized, phase 2a, non-inferiority trial

ABSTRACT A candidate AS01-adjuvanted vaccine containing four surface proteins from non-typable Haemophilus influenzae and Moraxella catarrhalis (NTHi-Mcat) has been developed to help prevent exacerbations of chronic obstructive pulmonary disease (COPD). Sequential administration of different vaccines containing the same AS01-adjuvant system could lead to immune interference. We compared administration of NTHi-Mcat following AS01-adjuvanted recombinant zoster vaccine (RZV) versus NTHi-Mcat alone. This phase 2a, open-label trial (NCT03894969) randomized healthy current or former smokers (50–80 years) without COPD to administration of NTHi-Mcat at 1, 3 or 6 months after RZV or to NTHi-Mcat alone (2-dose for both vaccines). Primary outcome was non-inferiority of the humoral immune response to NTHi-Mcat administered 1 month after RZV versus NTHi-Mcat alone, evaluated by specific antibody geometric mean concentration (GMC) ratio with 95% confidence intervals (CIs). The per-protocol set included 411 participants. Primary objective was met; lower limit of the 95%CI for the GMC ratio above 0.667 for all four vaccine antigens, 1 month after the second NTHi-Mcat dose. NTHi-Mcat induced similar immune response regardless of whether administered alone or 1, 3 or 6 months following RZV. Safety and reactogenicity profiles were acceptable; adverse event frequency was similar among study groups. Injection site pain was the most common symptom. No new safety concerns were identified. The study demonstrated non-inferiority of the immune response elicited by NTHi-Mcat administered sequentially to RZV versus NTHi-Mcat alone, indicating no immune interference. Starting from 1 month, no specific interval is required between RZV and NTHi-Mcat containing the same AS01-adjuvant system components in different quantities.