Universal Vaccination Strategy Research Articles

Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses.

Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity. It was shown to confer passive protection to piglets born to immunized sows. In mice, a single dose of GETV-3ΔS2-CM1 protected against infection with different strains of GETV, Semliki Forest virus, Ross River virus, o'nyong'nyong virus, chikungunya virus, and Barmah Forest virus. Chimaeras based on the GETV-3ΔS2-CM1 backbone maintained both the attenuated phenotype and high immunogenicity. The safety, efficacy, and ability to induce protection against multiple alphaviruses highlights the potential of GETV-3ΔS2-CM1 and chimaeras using this backbone as promising vaccine candidates. By contributing simultaneously to the wellbeing of animals and humans, our universal next generation vaccine strategy helps to achieve "One Health" goals.

What COVID-19 Vaccination Strategy Should Be Implemented and Which Vaccines Should Be Used in the Post-Pandemic Era?

COVID-19 vaccines have reduced the negative health and economic impact of the COVID-19 pandemic by preventing severe disease, hospitalizations and deaths. In the new socio-economic normality, the COVID-19 vaccination strategy can be universal or high-risk and seasonal or not seasonal, and different vaccines can be used. The universal vaccination strategy can achieve greater health and herd immunity effects and is associated with greater costs than the high-risk vaccination strategy. In each country, the optimal COVID-19 vaccination strategy must be decided by considering the advantages and disadvantages and assessing the costs, health effects and cost-effectiveness of the universal and high-risk vaccination strategies. The universal vaccination strategy should be implemented when the objective of the vaccination program is to achieve the greatest health benefits from COVID-19 vaccination and when its incremental cost-effectiveness ratio is lower than EUR 30,000-50,000 per QALY or LYG. The use of adapted vaccines targeting currently circulating variants of SARS-CoV-2 is necessary to avoid the immune escape of emerging variants.

Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine.

In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigated the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the "Knob-into-Hole" technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, elicited remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.

Updating and Refining of Economic Evaluation of Rotavirus Vaccination in Spain: A Cost-Utility and Budget Impact Analysis.

Two vaccines against rotavirus diseases, Rotarix® and RotaTeq®, are being marketed in Spain; but rotavirus is not presently among the diseases covered by universal vaccination in Spain. The aim of this study was to assess the efficiency of extending Spain's current targeted rotavirus vaccination strategy including only preterm babies, to a policy of universal vaccination. A de novo cohort-based Markov model was built to evaluate the efficiency of three compared rotavirus vaccination strategies in Spain: targeted, universal, and no vaccination. Using Rotarix® or RotaTeq®, we compared the cost-utility of these strategies from both a societal perspective and Spanish National Health System (SNHS) perspective. The model represents the most important clinical events conceivably linked to rotavirus infection. Efficacy, effectiveness, safety, costs, and utilities were identified by systematic reviews. Incremental cost-utility ratio (ICUR) is EUR 23,638/QALY (Quality-Adjusted Life Year) for targeted vaccination with Rotarix® compared with no vaccination. The ICUR for the rest of the strategies evaluated are above EUR 30,000/QALY. The sensitivity analysis shows price as the only parameter that could make the universal vaccination strategy efficient. Considering a threshold of EUR 25,000/QALY, only targeted vaccination with Rotarix® would be efficient from societal perspective. Price drops of 36.9% for Rotarix® and 44.6% for RotaTeq® would make universal vaccination efficient.

Projected Public Health Impact of a Universal Rotavirus Vaccination Program in France.

In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination. A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3. Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86-2.04 and 24.15-27.44, respectively. Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization.

Incidence and Nature of Short-Term Adverse Events following COVID-19 Second Boosters: Insights from Taiwan's Universal Vaccination Strategy.

This study evaluates the incidence and characteristics of adverse events (AEs) following the second COVID-19 booster dose, leveraging Taiwan's distinctive approach of extending booster vaccinations to all citizens, unlike the targeted high-risk group strategies in other countries. Utilizing data from Taipei Veterans General Hospital's Vaccine Adverse Event Reporting System (VAERS) from 27 October 2022 to 19 January 2023, this research examines AEs in 441 out of 1711 booster recipients, considering factors like age, vaccine brands, and booster combinations. The findings revealed incidence rates (IRs) of 25.6% (95% CI: 21.1-30.8) after the first booster and 24.9% (95% CI: 20.5-30.0) after the second, mostly non-serious, with those having AEs post-first booster being five times more likely to report them again (incidence rate ratio, 5.02, p < 0.001). Significantly, switching from the mRNA1273 vaccine to another brand reduced AE risk by 18%. This study underscores that AEs are more repetitive than cumulative with additional booster doses, advocating for personalized vaccination strategies based on individual medical histories and previous vaccine reactions. These insights are valuable for healthcare providers in discussing potential AEs with patients, thereby improving vaccine compliance and public trust, and for policymakers in planning future booster vaccination strategies.

Modeling hepatitis A epidemiological profiles and estimating the pediatric vaccination threshold in the Russian Federation.

To combat the hesitancy towards implementing a hepatitis A universal mass vaccination (UMV) strategy and to provide healthcare authorities with a comprehensive analysis of the potential outcomes and benefits of the implementation of such a vaccination program, we projected HAV seroprevalence and incidence rates in the total population of the Russian Federation and estimated the pediatric vaccination threshold required to achieve an incidence level of less than 1 case per 100,000 using a new mathematical model. A dynamic age-structured SEIRV (susceptible-exposed-infectious-recovered-vaccinated) compartmental model was developed and calibrated using demographic, seroprevalence, vaccination, and epidemiological data from different regions of the Russian Federation. This model was used to project various epidemiological measures. The projected national average age at the midpoint of population immunity increases from 40 years old in 2020 to 50 years old in 2036 and is shifted even further to the age of 70 years in some regions of the country. An increase of varying magnitude in the incidence of symptomatic HAV infections is predicted for all study regions and for the Russian Federation as a whole between 2028 and 2032, if the HAV vaccination coverage level remains at the level of 2022. The national average vaccination coverage level required to achieve a symptomatic HAV incidence rate below 1 case per 100,000 by 2032 was calculated to be 69.8% if children aged 1-6 years are vaccinated following the implementation of a UMV program or 34.8% if immunization is expanded to children aged 1-17 years. The developed model provides insights into a further decline of herd immunity to HAV against the background of ongoing viral transmission. The current favorable situation regarding hepatitis A morbidity is projected to be replaced by an increase in incidence rates if vaccination coverage remains at the current levels. The obtained results support the introduction of a hepatitis A UMV strategy in the Russian Federation.

Broad-spectrum vaccine via combined immunization routes triggers potent immunity to SARS-CoV-2 and its variants.

The development of broad-spectrum SARS-CoV-2 vaccines will reduce the global economic and public health stress from the COVID-19 pandemic. The use of conserved T-cell epitopes in combination with spike antigen that induce humoral and cellular immune responses simultaneously may be a promising strategy to further enhance the broad spectrum of COVID-19 vaccine candidates. Moreover, this research suggests that the combined vaccination strategies have the ability to induce both effective systemic and mucosal immunity, which may represent promising strategies for maximizing the protective efficacy of respiratory virus vaccines.

Characterizing the dynamics of BCR repertoire from repeated influenza vaccination

ABSTRACT Yearly epidemics of seasonal influenza cause an enormous disease burden around the globe. An understanding of the rules behind the immune response with repeated vaccination still presents a significant challenge, which would be helpful for optimizing the vaccination strategy. In this study, 34 healthy volunteers with 16 vaccinated were recruited, and the dynamics of the BCR repertoire for consecutive vaccinations in two seasons were tracked. In terms of diversity, length, network, V and J gene segments usage, somatic hypermutation (SHM) rate and isotype, it was found that the overall changes were stronger in the acute phase of the first vaccination than the second vaccination. However, the V gene segments of IGHV4-39, IGHV3-9, IGHV3-7 and IGHV1-69 were amplified in the acute phase of the first vaccination, with IGHV3-7 dominant. On the other hand, for the second vaccination, the changes were dominated by IGHV1-69, with potential for coding broad neutralizing antibody. Additional analysis indicates that the application of V gene segment for IGHV3-7 in the acute phase of the first vaccination was due to the elevated usage of isotypes IgM and IgG3. While for IGHV1-69 in the second vaccination, it was contributed by isotypes IgG1 and IgG2. Finally, 41 public BCR clusters were identified in the vaccine group, with both IGHV3-7 and IGHV1-69 were involved and representative complementarity determining region 3 (CDR3) motifs were characterized. This study provides insights into the immune response dynamics following repeated influenza vaccination in humans and can inform universal vaccine design and vaccine strategies in the future.

Universal varicella vaccination in Denmark: Modeling public health impact, age-shift, and cost-effectiveness.

We modeled the long-term clinical and economic impact of two-dose universal varicella vaccination (UVV) strategies in Denmark using a dynamic transmission model. The cost-effectiveness of UVV was evaluated along with the impact on varicella (including age-shift) and herpes zoster burden. Six two-dose UVV strategies were compared to no vaccination, at either short (12/15 months) or medium (15/48 months) intervals. Monovalent vaccines (V-MSD or V-GSK) for the 1st dose, and either monovalent or quadrivalent vaccines (MMRV-MSD or MMRV-GSK) for the 2nd dose were considered. Compared to no vaccination, all two-dose UVV strategies reduced varicella cases by 94%-96%, hospitalizations by 93%-94%, and deaths by 91%-92% over 50 years; herpes zoster cases were also reduced by 9%. There was a decline in the total number of annual varicella cases in all age groups including adolescents and adults. All UVV strategies were cost-effective compared to no vaccination, with ICER values ranging from €18,228-€20,263/QALY (payer perspective) and €3,746-€5,937/QALY (societal perspective). The frontier analysis showed that a two-dose strategy with V-MSD (15 months) and MMRV-MSD (48 months) dominated all other strategies and was the most cost-effective. In conclusion, all modeled two-dose UVV strategies were projected to substantially reduce the clinical and economic burden of varicella disease in Denmark compared to the current no vaccination strategy, with declines in both varicella and zoster incidence for all age groups over a 50-year time horizon.

Influenza vaccination-induced H3 stalk-reactive memory B-cell clone expansion

Current vaccine formulations elicit a recall immune response against viruses by targeting epitopes on the globular head of hemagglutinin (HA), and stalk-reactive antibodies are rarely found. However, stalk-specific memory B-cell expansion after influenza vaccination is poorly understood. In this study, B cells were isolated from individuals immunized with seasonal tetravalent influenza vaccines at days 0 and 28 for H7N9 stimulation in vitro. Plasma and supernatants were collected for the analysis of anti-HA IgG using ELISA and a Luminex assay. Memory B cells were positively enriched, and total RNA was extracted for B cell receptor (BCR) H-CDR3 sequencing. All subjects displayed increased anti-H3 antibody secretion after vaccination, whereas no increase in cH5/3-reactive IgG levels was detected. The number of shared memory B-cell clones among individuals dropped dramatically from 593 to 37. Four out of 5 subjects displayed enhanced frequencies of the VH3-23 and VH3-30 genes, and one exhibited an increase in the frequency of VH1-18, which are associated with the stalk of HA. An increase in H3 stalk-specific antibodies produced by B cells stimulated with H7N9 viruses was detected after vaccination. These results demonstrated that H3 stalk-specific memory B cells can expand and secrete antibodies that bind to the stalk in vitro, although no increase in serum H3 stalk-reactive antibodies was found after vaccination, indicating potential for developing a universal vaccine strategy.

Monophosphoryl lipid A-adjuvanted nucleoprotein-neuraminidase nanoparticles improve immune protection against divergent influenza viruses

Universal influenza vaccines are urgently needed to prevent recurrent influenza epidemics and inevitable pandemics. We generated double-layered protein nanoparticles incorporating two conserved influenza antigens—nucleoprotein and neuraminidase—through a two-step desolvation-crosslinking method. These protein nanoparticles displayed immunostimulatory properties to antigen-presenting cells by promoting inflammatory cytokine (IL-6 and TNF-α) secretion from JAWS II dendric cells. The nanoparticle immunization induced significant antigen-specific humoral and cellular responses, including antigen-binding and neutralizing antibodies, antibody- and cytokine (IFN-γ and IL-4)-secreting cells, and NP147–155 tetramer-specific cytotoxic T lymphocyte (CTL) responses. Co-administration of monophosphoryl lipid A (MPLA, a toll-like receptor 4 agonist) with the protein nanoparticles further improved immune responses and conferred heterologous and heterosubtypic influenza protection. The MPLA-adjuvanted nanoparticles reduced lung inflammation post-infection. The results demonstrated that the combination of MPLA and conserved protein nanoparticles could be developed into an improved universal influenza vaccine strategy.

Dynamic Changes in Hepatitis A Immunity in Regions with Different Vaccination Strategies and Different Vaccination Coverage.

The data on hepatitis A virus (HAV) seroprevalence are critical for the implementation of a universal mass vaccination (UMV) strategy. The latter has not been implemented in Russia; however, regional child vaccination programs have been adopted in some parts of the country. The aim of this study is to assess changes in HAV immunity within the last decade in regions of Russia with different vaccination strategies and different vaccination coverage rates. In regions where UMV has not been implemented and HAV vaccination coverage rates do not exceed the national average, the 50% seroprevalence threshold has shifted in the Moscow region from people aged under 40 years in 2008 to people aged over 59 years in 2020, and from people aged under 30 years to people aged over 40 years in the Khabarovsk region. In two regions (Yakutia and Sverdlovsk), a two-dose-based UMV scheme has been in place since 2011 and 2003, respectively, and in Tuva single-dose child immunization was launched in 2012. These regional programs have resulted in a significant increase in HAV seroprevalence in children and adolescents. In Yakutia, 50% herd immunity had been achieved by 2020 in age groups under 20 years, compared to 20–30% seroprevalence rates in 2008. In the Sverdlovsk region, HAV immunity has increased to >65% over the decade in children aged over 10 years, adolescents and young adults, whereas it declined in older age groups. However, a three-fold drop in HAV immunity has occurred in children under 10 years of age, reflecting a significant decline in vaccination coverage. In Tuva, HAV immunity rates in children under 10 years old increased two-fold to exceed 50% by 2020. These data suggest that UMV should be implemented on a national level. Measures to control vaccination coverage and catch-up vaccination campaigns are recommended in order to maintain the effectiveness of existing HAV vaccination programs.

Epigenetic adjuvants: durable reprogramming of the innate immune system with adjuvants.

Development of effective vaccines is a critical global health priority. Stimulating antigen-specific B and T cells to elicit long-lasting protection remains the central paradigm of vaccinology. Adjuvants are components that enhance vaccine immunogenicity by targeting specific innate immune receptors and pathways. Recent data highlight the capacity of adjuvants to induce durable epigenetic reprogramming of the innate immune system to engender heightened resistance against pathogens. This raises the prospect of developing epigenetic adjuvants that, in addition to stimulating robust T and B cell responses, convey broad protection against diverse pathogens by training the innate immune system. In this review, we discuss our emerging understanding of the various vaccines and adjuvants and their effects on durable reprogramming of the innate immune response, their putative mechanisms of action, and the promise and challenges of developing epigenetic adjuvants as a universal vaccine strategy.

Universal hepatitis B vaccination in adults aged 19–59 years: Updated recommendations of the advisory committee on immunization practices—United States, 2022

Universal hepatitis B vaccination in adults aged 19–59 years: Updated recommendations of the advisory committee on immunization practices—United States, 2022

Immunoinformatic paradigm predicts macrophage and T-cells epitope responses against globally conserved spike fragments of SARS CoV-2 for universal vaccination

BackgroundDifferent quickly-developed vaccines are introduced against COVID-19 with inconclusive results especially against some recent variants. Eventually, somewhere COVID-19 cases decline and in some countries it revived with some new mutant-variants (i.e. D614G, Delta and Omicron). ObjectivesProposing a universal vaccination strategy by screening globally-conserved SARS-CoV-2 spike-epitopes. MethodsPresently, several conserved (186-countries) sequences including multiple-variants (ClustalX2) epitopic-regions (SVMTriP and IEDB) and in-silico mutants of SARS-CoV-2 spike-protein-fragments (Cut1-4) were screened for their stability against proteases, antigenicity (VaxiJen V2.0 and for glycosylation effects NetOGlyc-NetNGlyc), MHCI/II reactivity (IEDB-TOOLS) and CD4+ responses by molecular-docking (Haddock2.4/PatchDock). We also examined Molecular-Dynamic-Simulation (myPresto verson-5) of MHC-II 3LQZ with 3-Cuts and T-cell 2-molecules (1KGC/4JRX) with SM3-Cut. The MD-simulation was run with 5000-cycles after 300 k-heating/1-atm pressure adjustment for the system-equilibration. Finally, 1000 fs production was run. ResultsThe cut4-mutant (SRLFRKSNLKPFERD) showed the highest combined-score 48.23548 and Immunogenicity-Score of 92.0887. The core-sequence SRLFRKSNL showed the highest Median-Percentile-Rank (7-HLA-allele) of 19. CD4+ immunogenicity also confirms the representation of the CUT4TM2 epitope SRLFRKSNL by MHC Class II. The epitope YNYKYRLFR from CUT4 showed an IC50 of ∼30 nM with allele HLA-DRB1*11:01 and HLA-DRB5*01:01 with plenty H-bonding. Cut4 double-mutants strongly interact with the exposed T-cell surface and are facilitated by its receptors. The MD-simulation data suggest that TM2 has a maximum RMSD value of 1.7 Å, DM2 is at 1.55 Å and SM3 is at 1.5 Å. These variations correspond to structural adjustments and involve binding/unbinding chemical interactions. The RMSD plot shows that 1KGC T-cell molecule is at 2.2 Å and the 4JRX is at 1.2 Å, which increases with the simulation time. ConclusionsScreening of conserved SARS-CoV-2 spike fragments helps to find the most stable antigenic-determinant which with some mutations showed better antigenicity. Further studies are necessary to develop global vaccination strategies against COVID-19.

A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination.

Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45HA2 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45HA2, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies.

PP167 Cost Effectiveness Of Universal Childhood Vaccination Against Hepatitis A

IntroductionHepatitis A (HA) is a liver disease with a low mortality rate, but it can cause debilitating symptoms and fulminant hepatitis in some cases. Its incidence is greater in geographical areas with poor sanitation and hygiene. Spain is considered a low-endemicity country, so universal childhood immunization against HA is currently not financed by the National Health System. The aim of this study was to synthesize the scientific evidence on the cost effectiveness of universal childhood vaccination against HA.MethodsFull economic evaluations, published in the English or Spanish languages, were included if they reported outcome measures related to the prevention of HA, adverse effects, or incremental cost-effectiveness ratios (ICERs). The Medline, Embase and Cochrane Library databases were searched for articles published from the beginning of the databases to April 2018.ResultsA total of 23 economic evaluations were included: one in a country of high endemicity, nine in countries of intermediate endemicity, and 13 in countries with low endemicity. Only one Spanish study, published in 1997, was found. Studies conducted in high- and intermediate- endemicity countries concluded that a universal childhood vaccination program against HA was a cost-effective option. However, in the case of countries with low endemicity the results were heterogeneous, although most agreed that a systematic vaccination strategy would not be a cost-effective option and that the adoption of such a strategy would not be justified given the limited benefits it would offer. The results of the economic evaluations depended on parameters such as the price and duration of the vaccine effect and the program coverage.ConclusionsIn countries with low endemicity the results were heterogeneous, although most studies concluded that the implementation of a universal vaccination strategy is not justified from the point of view of cost effectiveness.

Hepatitis A Outbreak Characteristics: A Comparison of Regions with Different Vaccination Strategies, Spain 2010-2018.

We compared the cumulative incidence and characteristics of hepatitis A outbreaks in two groups of Spanish autonomous regions according to whether a universal or risk group vaccination strategy was followed. Outbreaks between 2010 and 2018 were analyzed. The cumulative incidence rate of outbreaks was estimated and compared by estimating the rate ratio (RR). The characteristics of the outbreaks and those of the first cases were compared. Adjusted OR (aOR) were calculated using a multivariate logistic regression model. Outbreak incidence was 16.04 per million persons in regions with universal vaccination and 20.76 in those with risk-group vaccination (RR 0.77; 95%CI 0.62–0.94). Imported outbreaks accounted for 65% in regions with universal vaccination and 28.7% in regions with risk-group vaccination (aOR 3.88; 95%CI 2.13–7.09). Adolescents and young adults aged 15–44 years and men who have sex with men were less frequently the first case of the outbreak in regions with a universal vaccination strategy (aOR 0.54; 95%CI 0.32–0.92 and 0.23; 95%CI 0.07–0.82, respectively). The cumulative incidence rate of outbreaks was lower in regions with universal vaccination. In all regions, independently of the vaccination strategy, activities to vaccinate persons belonging to high-risk groups for infection should be emphasized.

Respiratory syncytial virus and influenza hospitalizations in Danish children 2010–2016

ObjectiveTo pave the way for universal or risk factor-based vaccination strategies, the present study aimed to describe the epidemiology and compare risk factors for hospitalization associated with respiratory syncytial virus (RSV) and influenza virus infections in Danish children. MethodsNational register-based cohort study among 403,422 Danish children born 2010–2016. ResultsPrior asthma hospitalization, number of children in the household, chronic disease and maternal history of asthma hospitalization were the most important risk factors for both RSV and influenza hospitalization. The incidence of influenza increased at school start. ConclusionsOur findings enable targeted vaccination programs for high-risk children with asthma-like disease, chronic disease, siblings in the household, or maternal history of asthma hospitalization.