Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

Background

The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?

Methods

We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.

Results

Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R₀ credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).

Conclusions

Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza. Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.

     

Evolving Epidemiology of Japanese Encephalitis: Implications for Vaccination

Purpose of Review

We examine the present global burden of Japanese encephalitis (JE) in endemic populations, summarize published cases in travelers since 2009, examine current guidelines for vaccination for international travelers, and consider challenges in prevention of this vector-borne disease.

Recent Findings

We identified 11 JE cases in travelers that were published in peer-reviewed literature since 2009. JE incidence in endemic countries appears to be declining but the number of JE cases reported to the World Health Organization (WHO) varied from estimates derived from other published reports based on serosurveys or sentinel surveillance. Current JE vaccines appear to be safe and are not associated with delayed hypersensitivity in contrast to the older mouse brain vaccine.

Summary

Given differences between WHO-reported cases and local surveillance data, future research on true incidence is needed. Regular assessment will inform JE risk in travelers. National and international guidelines on JE vaccination varied; we suggest areas for improvement.

     

Predictors of seasonal influenza vaccination in chronic asthma

Background

Guidelines advise annual influenza vaccination in chronic asthma. The aim of this study was to determine uptake of the influenza vaccine in a group of patients (n?=?146) with moderate to severe chronic asthma and establish the main predictors of vaccination.

Method

Patients attending a hospital asthma clinic were asked to complete a questionnaire in February 2012 (n?=?146). These same patients were contacted a year later via telephone (n?=?109 responded), and they were asked to complete the same questionnaire.

Results

Vaccination rate was 50.3% in winter 2011/12, and 57.8% in 2012/13. Using binary logistic regression, the predictors for vaccination in 2012 were patient advice (Odds ratio [OR] 15.37 p?=?0.001), female gender (OR 2.75, p?=?0.028), past side effects (OR 0.21, p?=?0.001) and comorbidity (OR 0.39, p?=?0.013). Stepwise regression resulted in age as predictor (T value?=?3.99, p?=?0.001). On analyzing the responses from the second questionnaire at one year after attendance to asthma clinic, predictors changed to compliance to medication (OR 9.52, p= 0.001) and previous exacerbations (OR 4.19, p?=?0.026). Out of the 56 patients vaccinated in 2011/12, 33 reported asthma exacerbations before 2012, and 29 reported asthma exacerbations after receiving the influenza vaccine. Out of the 46 unvaccinated patients in 2012, 27 had asthma exacerbations before 2012 and 19 patients had exacerbations in 2013. Patients vaccinated in 2011/12 needed 0.59 courses of steroid/patient/year, and 1.23 visits for nebulizer/patient/year while non-vaccinated patients needed 0.18 courses of steroids/patient/year (p?=?0.048), and 0.65 visits for nebulized/patient/year (p?=?0.012). Patients’ subjective statements broadly confirmed the predictors. 16/69 (23.1%) received the vaccine in winter 2012/13 despite reporting previous side effects.

Conclusions

Advice to patient, female gender and patients’ age predicted vaccination, while past side effects to the influenza vaccine, and presence of comorbidities predicted non vaccination. Symptomatic asthma patients are more likely to be vaccinated. One year after the first contact, treatment compliance and previous asthma exacerbations gained statistical significance as predictors of vaccination.

     

Seasonal dynamics of influenza in Brazil: the latitude effect

Background

Influenza is a global transmissible disease. Its dynamics is far better understood in temperate climates than in the tropics. We aim to close this knowledge gap between tropical and temperate regions by showing how the influenza seasonality evolves in Brazil, a tropical country that encompasses a wide range of latitudes and six climatic sub-types.

Methods

We analyzed a state-level, weekly Syndrome of Acute Respiratory Disease (SARI) incidence data ranging from 2010 to 2016. We combined two techniques hierarchically: first the wavelet decomposition technique to detect annual periodicity and then circular statistics to describe seasonal measures of the periodic states.

Results

We found significant annual periodicity in 44% of the states. For these, we calculated several seasonal measures such as the center of gravity or mean timing of activity. The relationship between the seasonal signatures and latitude was clear and statistically significant. States with seasonal signature are clustered along the coast. Most Amazonian and Central West states exhibit no seasonal behavior. Among the seasonal states, influenza starts in Northeast region, spreading southbound.

Conclusions

Our study advances the comprehension of influenza seasonality in tropical areas and could be used to design more effective prevention and control strategies.

     

New Advances in Hepatitis B Vaccination for Adults

Purpose of Review

The mainstay of elimination of hepatitis B virus is through primary prevention by vaccination recommended by the World Health Organization. This review seeks to update readers on the performance of the current second-generation vaccine and the challenges including primary and secondary vaccine failure, as well as compliance and coverage.

Recent Findings

Primary vaccine failure in children may be overcome by HBIG and antiviral therapy in high-risk pregnancies, while in adults, a number of strategies to address this include intradermal delivery, double-dose vaccination, improved adjuvants, and a third-generation vaccine with pre-S1 and pre-S2 proteins. However, there is still no accepted standard therapy for primary vaccine failure. Secondary vaccine failure is less problematic with 3.9% of vaccines developing anti-HBc antibody, but only one reported case of chronicity has developed after vaccination.

Summary

The current second-generation prophylactic hepatitis B vaccines have performed extremely well, but there remain some challenges with regard to vaccine failure. A number of different strategies have been used to overcome this. Overall vaccine failure constitutes a relatively small proportion of vaccinees.

     

Zoonotic Influenza and Human Health—Part 2: Clinical Features,Diagnosis, Treatment,and Prevention Strategies

Purpose of Review

Zoonotic influenza viruses are those influenza viruses that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this second part of a two-part review, we discuss the clinical features, diagnostic modalities, and treatment of zoonotic influenza, and provide an overview of prevention strategies.

Recent Findings

Illnesses caused by novel reassortant avian influenza viruses continue to be detected and described; most recently, a human case of avian influenza A(H7N4) has been described from China. We continue to witness increasing rates of A(H7N9) infections, with the latest (fifth) wave, from late 2016 to 2017, being the largest to date. The case fatality rate for A(H7N9) and A(H5N1) infections among humans is much higher than that of seasonal influenza infections. Since the emergence of the A(H1N1) 2009 pandemic, and subsequently A(H7N9), testing and surveillance for novel influenzas have become more effective. Various newer treatment options, including peramivir, favipiravir (T-705), and DAS181, and human or murine monoclonal antibodies have been evaluated in vitro and in animal models.

Summary

Armed with robust diagnostic modalities, antiviral medications, vaccines, and advanced surveillance systems, we are today better prepared to face a new influenza pandemic and to limit the burden of zoonotic influenza than ever before. Sustained efforts and robust research are necessary to efficiently deal with the highly mutagenic zoonotic influenza viruses.

     

Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD<Subscript>65</Subscript>-induced immune response

Aims/hypothesis

A European Phase III trial of GAD formulated with aluminium hydroxide (GAD-alum) failed to reach its primary endpoint (preservation of stimulated C-peptide secretion from baseline to 15 months in type 1 diabetes patients), but subgroup analysis showed a clinical effect when participants from Nordic countries were excluded, raising concern as to whether the mass vaccination of the Swedish and Finnish populations with the Pandemrix influenza vaccine could have influenced the study outcomes. In the current study, we aimed to assess whether Pandemrix vaccination affects the specific immune responses induced by GAD-alum and the C-peptide response.

Methods

In this secondary analysis, we analysed data acquired from the Swedish participants in the Phase III GAD-alum trial who received subcutaneous GAD-alum vaccination (two doses, n = 43; four doses, n = 46) or placebo (n = 48). GAD autoantibodies (GADA) and H1N1 autoantibodies, GAD₆₅-induced cytokine secretion and change in fasting and stimulated C-peptide levels from baseline to 15 months were analysed with respect to the relative time between H1N1 vaccination and the first injection of GAD-alum.

Results

GADA levels at 15 months were associated with the relative time between GAD-alum and Pandemrix administration in participants who received two doses of the GAD-alum vaccine (p = 0.015, r = 0.4). Both in participants treated with two doses and four doses of GAD-alum, GADA levels were higher when the relative time between vaccines was ≥210 days (p < 0.05). In the group that received two doses of GAD-alum, levels of several GAD₆₅-induced cytokines were higher in participants who received the H1N1 vaccination and the first GAD-alum injection at least 150 days apart, and the change in fasting and stimulated C-peptide at 15 months was associated with the relative time between vaccines. Neither of these effects were observed in individuals who received four doses of GAD-alum.

Conclusions/interpretation

In individuals who received two doses of GAD-alum, receiving the Pandemrix vaccine closer to the first GAD-alum injection, i.e. <150 days, seemed to affect both GAD₆₅-induced immune response and C-peptide preservation.

Trial registration:

ClinicalTrials.gov NCT00723411.

     

Rotavirus epidemiology and vaccine demand: considering Bangladesh chapter through the book of global disease burden

Background

Rotavirus is the major cause of gastroenteritis in children throughout the world. Every year, a large number of children aged < 5 years die from rotavirus-related diarrhoeal diseases. Though these infections are vaccine-preventable, the vast majority of children in low-income countries suffer from the infection. The situation leads to severe economic loss and constitutes a major public health problem.

Methods

We searched electronic databases including PubMed and Google scholar using the following words: “features of rotavirus,” “epidemiology of rotavirus,” “rotavirus serotypes,” “rotavirus in Bangladesh,” “disease burden of rotavirus,” “rotavirus vaccine,” “low efficacy of rotavirus vaccine,” “inactivated rotavirus vaccine”. Publications until July 2017 have been considered for this work.

Results and conclusion

Currently, two live attenuated vaccines are available throughout the world. Many countries have included rotavirus vaccines in national immunization program to reduce the disease burden. However, due to low efficacy of the available vaccines, satisfactory outcome has not yet been achieved in developing countries such as Bangladesh. Poor economic, public health, treatment, and sanitation status of the low-income countries necessitate the need for the most effective rotavirus vaccines. Therefore, the present scenario demands the development of a highly effective rotavirus vaccine. In this regard, inactivated rotavirus vaccine concept holds much promise for reducing the current disease burden. Recent advancements in developing an inactivated rotavirus vaccine indicate a significant progress towards disease prophylaxis and control.

     

Development of universal influenza vaccines based on influenza virus M and NP genes

Purpose

Vaccination is the safest and most effective measure against influenza virus infections. However, traditional influenza vaccines cannot respond effectively to an unforeseen epidemic or pandemic caused by a virus with antigenic drifts or antigenic shifts. Therefore, developing a universal influenza vaccine (UIV) that induces broad-spectrum and long-term immunity has become a major trend in influenza vaccine research and development.

Methods

This article reviews the development of UIVs based on these conserved influenza virus proteins.

Results and Conclusion

The matrix protein (M1, M2) and nucleoprotein (NP) of influenza viruses have highly conserved sequences, and they become the major target antigens of current UIV studies.     

Socio‐demographic differences in opinions about 2009 pandemic influenza A (H1N1) and seasonal influenza vaccination and disease among adults during the 2009–2010 influenza season

Background In April 2009, a novel influenza A virus emerged in the United States. By the end of July, influenza A (H1N1) 2009 monovalent (2009 H1N1) vaccine had been developed, licensed, and recommended by the Advisory Committee on Immunization Practices. Initial target groups for vaccination were identified and the first vaccine was publicly available in early October 2009. Objective This study examines socio‐demographic differences in opinions about 2009 pandemic influenza A (H1N1) (pH1N1) and seasonal influenza disease and vaccines and the association with receipt of influenza vaccinations during the 2009–2010 influenza season. Changes in opinions over the course of the pH1N1 pandemic were also examined. Methods Data from the 2009 National H1N1 Flu Survey (NHFS) were analyzed. The NHFS was a CDC‐sponsored telephone survey initiated in response to the 2009 pH1N1 pandemic to obtain weekly within‐season estimates of vaccination coverage, opinions, and other information. Results Opinions about influenza vaccine and disease varied significantly by race/ethnicity, income, and education level. In multivariable logistic regression analysis, adjusted 2009 H1N1 vaccination coverage was most strongly associated with opinions about the effectiveness of the vaccine and personal risk of disease, varying from 7 to 11% among adults who believed the vaccine to have low effectiveness and themselves at low risk of influenza, to 50–53% among those who thought vaccine effectiveness to be high and themselves at high risk of influenza. Conclusion Improving communication about personal risk and the effectiveness of influenza vaccines may improve vaccination coverage. The findings of difference in opinions could be used to target communication.     

A case of acute hepatitis A infection in an HIV-positive patient despite complete hepatitis A vaccination

Background

Vaccination against hepatitis A virus infection is recommended for men who have sex with men and other risk groups. The protection offered by the combined hepatitis A and B vaccine is comparable to that offered by the monovalent hepatitis A vaccine.

Case

A 38-year-old HIV-positive patient presented with right upper abdominal pain, fever and jaundice. Serological work-up and detection of hepatitis A RNA in stool sample revealed an acute hepatitis A infection despite a previous complete vaccination with the combined hepatitis A and B vaccine.

Conclusion

Although the combined hepatitis A and B vaccine is associated with very good seroconversion rates, the effectiveness in HIV-positive patients is not ensured, even in cases with CD4 cell counts of > 500/μl. Therefore, regular post-vaccine testing should be encouraged to assess seroconversion in immunocompromised subjects.

     

Prevalence of antibodies and humoral response after seasonal trivalent vaccination against influenza B lineages in an elderly population of Spain

Introduction

The aim of this study was to analyze the presence of antibodies against both Yamagata and Victoria influenza B lineages and to check the response after seasonal trivalent vaccination.

Therapeutic Vaccines for Hypertension: a New Option for Clinical Practice

Purpose of Review

Vaccines are commonly used as preventive methods, primarily against infectious diseases. The goal of our study is to develop the therapeutic vaccine for hypertension.

Recent Findings

We and others recently reported that an angiotensin II (AngII) vaccine for hypertension successfully attenuated elevated blood pressures in an animal model without any immunogenic side effects. In this system, an immunogenic molecule (i.e., KLH) with adjuvants provides an antigen that supports the activation of helper T cells. In addition, pretreatment with the AngII vaccine exerts neuroprotective effects in a cerebral ischemia model and cardioprotective effects in a myocardial infarction model. In the early phase of clinical trial, the administration of an AngII vaccine (AngQb-Cyt006) successfully decreased blood pressure in hypertensive patients with the increase of anti-AngII antibody titer.

Summary

Increasing the effectiveness of drug adherence interventions in the clinical setting may have a large impact on the health of the population, which can be improved by using successful therapeutic vaccines. In this review, we describe the concept of therapeutic vaccines for hypertension and future directions for therapeutic vaccines.

     

Zoonotic Influenza and Human Health—Part 1: Virology and Epidemiology of Zoonotic Influenzas

Purpose of Review

Zoonotic influenza viruses are those that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. They have also been implicated in the causation of deadly pandemics in recent history. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this first part of a two-part review, we describe the structure of zoonotic influenza viruses, the relationship between mutation and pandemic capacity, pathogenesis of infection, and also discuss history and epidemiology.

Recent Findings

We are currently witnessing the fifth and the largest wave of the avian influenza A(H7N9) epidemic. Also in circulation are a number of other zoonotic influenza viruses, including avian influenza A(H5N1) and A(H5N6); avian influenza A(H7N2); and swine influenza A(H1N1)v, A(H1N2)v, and A(H3N2)v viruses. Most recently, the first human case of avian influenza A(H7N4) infection has been documented.

Summary

By understanding the virology and epidemiology of emerging zoonotic influenzas, we are better prepared to face a new pandemic. However, continued effort is warranted to build on this knowledge in order to efficiently combat the constant threat posed by the zoonotic influenza viruses.

     

Whole genome sequencing identifies influenza A H3N2 transmission and offers superior resolution to classical typing methods

Objectives

Influenza with its annual epidemic waves is a major cause of morbidity and mortality worldwide. However, only little whole genome data are available regarding the molecular epidemiology promoting our understanding of viral spread in human populations.

Methods

We implemented a RT-PCR strategy starting from patient material to generate influenza A whole genome sequences for molecular epidemiological surveillance. Samples were obtained within the Bavarian Influenza Sentinel. The complete influenza virus genome was amplified by a one-tube multiplex RT-PCR and sequenced on an Illumina MiSeq.

Results

We report whole genomic sequences for 50 influenza A H3N2 viruses, which was the predominating virus in the season 2014/15, directly from patient specimens. The dataset included random samples from Bavaria (Germany) throughout the influenza season and samples from three suspected transmission clusters. We identified the outbreak samples based on sequence identity. Whole genome sequencing (WGS) was superior in resolution compared to analysis of single segments or partial segment analysis. Additionally, we detected manifestation of substantial amounts of viral quasispecies in several patients, carrying mutations varying from the dominant virus in each patient.

Conclusion

Our rapid whole genome sequencing approach for influenza A virus shows that WGS can effectively be used to detect and understand outbreaks in large communities. Additionally, the genomic data provide in-depth details about the circulating virus within one season.

     

Pandemic influenza is a strong motivator for participation in vaccine clinical trials among HIV-positive Canadian adults

BACKGROUND:

HIV-positive patients represent an immunosuppressed population at risk for severe influenza. In the event of a pandemic, such as 2009 H1N1, rapid implementation of vaccine clinical trials in target populations will be critical. In the present paper, knowledge and attitudes of HIV-positive adults regarding seasonal/pandemic influenza vaccination were evaluated, and facilitators and barriers to participation in vaccine clinical trials were explored.

METHODS:

A validated, 70-item, self-administered questionnaire was distributed to all HIV patients presenting for routine follow-up at eight Canadian Institutes of Health Research Canadian HIV Trials Network (CTN) sites from October 2008 to February 2009, as well as all participants in CTN trial 237. This study has representation from all Canadian provinces.

RESULTS:

In total, 610 HIV-positive adults responded (298 CTN 237 participants; 312 non-CTN 237 participants). Most reported receiving influenza vaccine last season (83% of CTN 237 participants versus 83% non-CTN 237 participants; P not significant) and most would receive a pandemic influenza vaccine if offered (76% versus 73%; P not significant). A majority believed that it was important to include HIV patients in vaccine clinical trials (65% versus 53%; P<0.001) and would agree to participate in trials of a pandemic vaccine if invited (86% versus 51%; P≤0.0001). Predictors of willingness to participate in a pandemic vaccine trial were ‘desire to be protected from pandemic flu’, OR 4.5 (95% CI 2 to 8) and ‘desire to help others’, OR 2.3 (95% CI 1.3 to 4.5). ‘Fear of needles’, OR 0.49 (95% CI 0.1 to 1.5) and ‘need for extra blood tests’, OR 0.49 (95% CI 0.2 to 1.4) were key barriers to participation.

CONCLUSION:

Most HIV-positive Canadian adults surveyed receive influenza vaccination. Protection from pandemic influenza is considered important and is a motivator for receiving influenza vaccine and future trial participation. Modifiable barriers to these objectives identified in the present study should be the focus of efforts to increase influenza immunization in this population.     

Incremental Cost-Effectiveness of 13-valent Pneumococcal Conjugate Vaccine for Adults Age 50 Years and Older in the United States

BACKGROUND

Recently released results from a randomized controlled trial have shown that 13-valent pneumococcal conjugate vaccine (PCV13) is efficacious against vaccine-type nonbacteremic pneumonia in adults.

OBJECTIVE

We examined the incremental cost-effectiveness of adding PCV13 to the Advisory Committee on Immunization Practices (ACIP) adult immunization schedule.

METHODS

We used a probabilistic model following cohorts of 50-, 60-, or 65-year-olds. We used separate vaccination coverage and disease incidence data for healthy and high-risk adults. Incremental cost-effectiveness ratios were determined for each potential vaccination strategy.

RESULTS

In the base case scenario, our model indicated that adding PCV13 at age 65 or replacing 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 with PCV13 provided more value for money than adding PCV13 at ages 50 or 60. After projections of six additional years of herd protection from the childhood immunization program were incorporated, we found adding PCV13 dominated replacing PPSV23. For a cohort of 65-year-olds in 2013, the cost of adding PCV13 at age 65 to the schedule was $62,065 per quality-adjusted life year (QALY) gained, which rose to $272,621 after 6 years of projected herd protection.

CONCLUSION

The addition of one dose of PCV13 for adults appears to have a cost-effectiveness ratio comparable to other vaccination interventions in the short run, though anticipated herd protection from the childhood immunization program may dramatically increase the cost per QALY after only a few years.

     

Robust and prototypical immune responses toward influenza vaccines in the high-risk group of Indigenous Australians

Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigenous people globally. Although vaccination against influenza is recommended for those most at risk, studies on immune responses elicited by seasonal vaccines in Indigenous populations are largely missing, with no data available for Indigenous Australians and only one report published on antibody responses in Indigenous Canadians. We recruited 78 Indigenous and 84 non-Indigenous Australians vaccinated with the quadrivalent influenza vaccine into the Looking into InFluenza T cell immunity - Vaccination cohort study and collected blood to define baseline, early (day 7), and memory (day 28) immune responses. We performed in-depth analyses of T and B cell activation, formation of memory B cells, and antibody profiles and investigated host factors that could contribute to vaccine responses. We found activation profiles of circulating T follicular helper type-1 cells at the early stage correlated strongly with the total change in antibody titers induced by vaccination. Formation of influenza-specific hemagglutinin-binding memory B cells was significantly higher in seroconverters compared with nonseroconverters. In-depth antibody characterization revealed a reduction in immunoglobulin G3 before and after vaccination in the Indigenous Australian population, potentially linked to the increased frequency of the G3m21* allotype. Overall, our data provide evidence that Indigenous populations elicit robust, broad, and prototypical immune responses following immunization with seasonal inactivated influenza vaccines. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and their subsequent complications.

Influenza is a significant respiratory viral infection that causes a serious burden of disease. High morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in specific high-risk population groups, including children, the elderly, pregnant women, Indigenous people globally, and individuals with underlying comorbidities such as diabetes, immunosuppression, and lung and heart disease (1–3). Currently, antibody-based influenza vaccines targeting highly variable hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins are the most effective way to combat seasonal infections. The inactivated influenza vaccine contains glycoproteins corresponding to the circulating A/H3N2 and A/H1N1 strains and one B strain from either the Victoria or Yamagata lineage (in trivalent/TIV vaccines) or both B lineage strains (in quadrivalent/QIV vaccines). Antigenic drift necessitates annual updates of the vaccine components to warrant protection, and despite this the overall vaccine effectiveness can vary vastly from −7 to 75% (4). Vaccine effectiveness not only differs between seasons but also between vaccine components, with H3N2 showing the lowest overall vaccine effectiveness and H1N1pdm09 (pH1N1) the highest (5). Several factors such as preexisting immunity, immunosenescence, and vaccine strain mismatch can influence vaccine effectiveness (6). Genetic factors such as HLA polymorphisms contributing to differences in HLA-II expression are associated with stronger or weaker vaccine responses (7). For example, individuals expressing HLA-DRB1*11:04 showed high titers postvaccination whereas HLA-DRB1*13:01 showed reduced antibody titers postvaccination (7).Our understanding of why some individuals fail to establish a protective immune response after influenza vaccination is still very limited. To determine which factors shape the immune response postvaccination, we and others have identified cellular and humoral responses that correlate with robust immune responses to influenza vaccination (8, 9). Importantly, 7 d postvaccination an increase in ICOS⁺CXCR3⁺CXCR5⁺CD4⁺ circulating T follicular helper 1 (cT_FH1) cells was observed that correlated with antibody-secreting cells (ASCs) and rises in antibody titers (9, 10).Indigenous populations experience higher rates of infections with a range of pathogens including tuberculosis (11) and influenza (12). Notification and hospitalization rates of seasonal influenza virus infections are 1.5 to 8.6 times and 1.2 to 4.3 times, respectively, higher in Indigenous compared with non-Indigenous Australians (12). With social determinants of health and comorbidities contributing to a higher disease burden (13), one key strategy proposed to improve health outcomes for Indigenous populations is immunization (14). However, only a few studies to date have examined viral immunity in Indigenous populations and most of our knowledge is based on studies in non-Indigenous populations. We have revealed host variations in HLA profiles in Indigenous populations (15, 16), suggesting that differences in HLA or other genetic factors might impact influenza vaccine responses in Indigenous Australians. Despite national funding, vaccination rates still remain low in Indigenous communities (17). A recent study from Menzies et al. revealed that more than 50% of unvaccinated Indigenous Australians stated that the “flu” vaccine would not be effective (18). To date, there are no published data to define immune responses to influenza vaccines in Indigenous Australians, while globally only one study assessed antibody responses following adjuvanted pH1N1 influenza immunization in Indigenous Canadians and showed comparable antibody levels pre- and postvaccination (19). Determining the immunological response to influenza vaccination in high-risk Indigenous populations can therefore provide a stronger scientific basis for influenza recommendations, which if appropriately communicated may increase vaccine uptake.In this study, we recruited Indigenous and non-Indigenous Australians vaccinated with the QIV between 2016 and 2018 and assessed their immunity pre- and postvaccination. We performed in-depth analyses of T and B cell activation, memory B cell formation, and antibody profiles as well as investigating host factors that could contribute to vaccine responses. Our study clearly demonstrates that Indigenous Australians mount effective and prototypical immune responses to the inactivated influenza vaccine and thus provides an immunological basis to support current vaccine recommendations in Indigenous populations.     

Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.