Innovative Vaccine Research Articles

Behavioral Health, Nursing Home Workforce, And More

From the Editor-In-Chief Health AffairsVol. 42, No. 2: Behavioral Health, Nursing Home Workforce & More Behavioral Health, Nursing Home Workforce, And MoreAlan R. WeilPUBLISHED:February 2023Free Accesshttps://doi.org/10.1377/hlthaff.2023.00023AboutSectionsView PDFPermissions ShareShare onFacebookTwitterLinked InRedditEmail ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsDownload Exhibits TOPICSBehavioral health careNursing homesWorkforce issuesEmergency departmentsTelehealthHealth equityThe February issue of Health Affairs covers behavioral health, including mental health and substance use; the nursing home workforce; and health equity issues such as racial and ethnic disparities in ambulance transportation destinations and adverse birth outcomes.Behavioral HealthIn the midst of a mental health provider shortage, Lisa Rotenstein and coauthors find an almost 50 percent increase in the share of primary care physician visits that address a mental health concern, with growth from 10.7 percent of visits in 2006–07 to 15.9 percent in 2016 and 2018. Black patients and Hispanic patients are 40 percent less likely than White patients and non-Hispanic patients, respectively, to have a mental health concern addressed during a primary care visit.K. John McConnell and colleagues use newly available national Medicaid claims data from 2018 to examine emergency department (ED) visits for mental health conditions among Medicaid beneficiaries. They report substantial state-to-state variation “both in ED visits for mental health conditions and in outpatient mental health visits, with these measures positively correlated.”Lori Uscher-Pines and coauthors explore recent trends in the use of telemedicine to address opioid use disorder (OUD). More than three-quarters of clinicians treating OUD report the use of one or more digital equity strategies designed to address barriers patients may have to using telemedicine, with about one-third offering real-time technical assistance and more than 15 percent supplying patients with electronic devices if they do not have them.Brendan Saloner and coauthors investigate smoking rates among people involved in the criminal legal system—a group of people with relatively high rates of smoking and substance use disorder (SUD). Using data from the period 2010–19, the authors find that “overall smoking rates among people with SUD decreased by 9.4 percentage points…during the study period, but they remained effectively unchanged in the subgroup of people with SUD who had criminal legal involvement.”Nursing Home WorkforceUsing a novel database of real estate investment trust (REIT) investments in US nursing homes and Medicare cost data from the period 2013–19, Robert Tyler Braun and coauthors determine that REIT investment in a nursing home increased licensed practical nurse and certified nursing assistant staffing hours per resident day by 2.15 percent and 1.55 percent, respectively, while decreasing registered nurse staffing in years 2 and 3 after investment.Elizabeth White and coauthors explore the relationship between nursing home staff shift times and COVID-19 testing and vaccination status. They find that day-shift staff had the highest testing rates and odds of vaccination, whereas night-shift staff had the lowest.Adequate staffing is central to ensuring high nursing home quality. To help illuminate the implications of various policy recommendations, John Bowblis and coauthors analyze nursing home staff expenditures and determine that “any specific threshold for nursing staff expenditures…would have a varying degree of effectiveness in ensuring that any given nursing home was adequately staffed.” Ultimately, the authors argue, increased expenditures on staff do not necessarily translate to an increase in staffing levels.EquityChristine Pack and coauthors investigate ambulance destinations for patients transported in 2020 from the same ZIP code and find meaningful differences by race and ethnicity. “In half of the studied ZIP codes, at least 8 percent of White patients would have had to be transported to different hospitals to achieve evenness in the transport destinations of White and non-White patients,” the authors report.Clare Brown and coauthors examine disparities in rates of preterm birth and low birthweight across racial and ethnic subcategories. They find sizable variation in adverse birth outcomes within racial and ethnic groups, demonstrating that broad racial and ethnic categorizations can conceal important intragroup differences.Eunhae Grace Oh and coauthors analyze dialysis facility networks for Medicare Advantage (MA) plans in 2020, one year before changes that significantly increased MA enrollment among patients with end-stage renal disease (ESRD). Nearly one-quarter of dialysis networks were narrow, which the authors define as including 25 percent or less of the dialysis facilities within the plan’s service area. Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native beneficiaries with ESRD were more likely than White beneficiaries to be enrolled in narrow-network MA plans.Examining COVID-19 booster rates at the end of the first Omicron wave in 462 Massachusetts communities, Adam Gaffney and coauthors find lower rates in communities with higher uninsurance rates and lower prevalence of medical checkups, after controlling for demographic factors. They call for “innovative vaccination outreach efforts to communities with a high prevalence of chronic illness…to mitigate the inequitable burden of COVID-19.” Loading Comments... Please enable JavaScript to view the comments powered by Disqus. DetailsExhibitsReferencesRelated Article Metrics History Published online 6 February 2023 Information© 2023 Project HOPE—The People-to-People Health Foundation, Inc.PDF download

A perspective on SARS-CoV-2 virus-like particles vaccines.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China, in December 2019. The 2019 coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, has spread to almost all corners of the world at an alarming rate. Vaccination is important for the prevention and control of the COVID-19 pandemic. Efforts are underway worldwide to develop an effective vaccine against COVID-19 using both traditional and innovative vaccine strategies. Compared to other vaccine platforms, SARS-CoV-2 virus-like particles （VLPs ）vaccines, as a new vaccine platform, have unique advantages: they have artificial nanostructures similar to natural SARS-CoV-2, which can stimulate good cellular and humoral immune responses in the organism; they have no viral nucleic acids, have good safety and thermal stability, and can be mass-produced and stored; their surfaces can be processed and modified, such as the adjuvant addition, etc.; they can be considered as an ideal platform for COVID-19 vaccine development. This review aims to shed light on the current knowledge and progress of VLPs vaccines against COVID-19, especially those undergoing clinical trials.

Development and Assessment of Innovative High-Fidelity Simulation Vaccination Course Integrating Emergency Cases for Pharmacy Undergraduates-A Randomized Controlled Study.

Recently, pharmacists in Germany were allowed to administer influenza and COVID-19 vaccines for people aged 12 years and older in order to increase vaccination coverage rates. In order to adapt the pharmacy curriculum for clinical practice, an innovative, vaccination training course using a high-fidelity simulator (HFS) was developed, implementing clinical scenarios to manage adverse events. In a randomized controlled trial using a pre and post design with pharmacy undergraduates, the intervention group interacted with an HFS, while the control group was trained with low-fidelity injection pads. Before and after the respective training, each participant went through an objective structured clinical examination (OSCE) and completed a self-assessment questionnaire and knowledge quiz. Both training methods showed a significant increase in skills, but there was also a significant greater increase in the intervention group when compared to the control group, particularly with respect to the vaccination process. Furthermore, every individual in the intervention group improved from the pre- to post-training OSCEs. Therefore, HFS has been proven to be an appropriate tool to train pharmacy students for the purposes of vaccine administration and to prepare for future challenges. Particularly, recognizing and managing adverse reactions can be addressed in a very effective way.

DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning.

The SARS-CoV-2 pandemic has demonstrated the need to create highly effective antivirals and vaccines against various RNA viruses, including SARS coronaviruses. This paper provides a short review of innovative strategies in the development of antivirals and vaccines against SARS coronaviruses, with a focus on antisense antivirals, oligonucleotide adjuvants in vaccines, and oligonucleotide vaccines. Well-developed viral genomic databases create new opportunities for the development of innovative vaccines and antivirals using a post-genomic platform. The most effective vaccines against SARS coronaviruses are those able to form highly effective memory cells for both humoral and cellular immunity. The most effective antivirals need to efficiently stop viral replication without side effects. Oligonucleotide antivirals and vaccines can resist the rapidly changing genomic sequences of SARS coronaviruses using conserved regions of their genomes to generate a long-term immune response. Oligonucleotides have been used as excellent adjuvants for decades, and increasing data show that oligonucleotides could serve as antisense antivirals and antigens in vaccine formulations, becoming a prospective tool for immune system tuning.

Innovation sharing a remedial measure: the case of Covid-19 pandemic

PurposeThis study has aimed to analyse the role of innovation-sharing collaboration in the large-scale manufacturing of Covid-19 vaccination across the globe and its impact on the mortality rate of the countries where the pharmaceutical manufacturers received such innovation.Design/methodology/approachThe authors have relied upon the difference-in-difference (DID) approach by utilizing the data available on public platforms such as World Health Organization (WHO) databank, organization for economic co-operation and development (OECD) data bank, istat, Indian bureau of statistics and European centre for disease prevention and control (ecdc) from 2020 to 2021 to establish the empirical inference of the analysis.FindingsThis study’s results present that after the invention and commercialization of the vaccine, the Covid-19 impact was still intact and people were dying continuously. However, it was impossible to fulfil the demand of the 7 billion population in a short time. In the light of these facts, the WHO encouraged sharing vaccine innovation with other countries to enhance production capacity. The authors found that after vaccine innovation sharing, Covid-19’s devastation slowed: the fatality rate was marginally reduced, and economic conditions started their recovery journey.Originality/valueThis study’s findings present that the Covid-19 vaccine played a pivotal role in tackling the Covid-19’s devastating impact on the entire world. It emphasizes the role of innovation-sharing collaborations in curtailing hazardous consequences, including the mortality rate during a crisis, and such collaborations’ impact on the countries where institutions involved in them reside.

The pH-responsive zeolitic imidazolate framework nanoparticle as a promising immune-enhancing adjuvant for anti-caries vaccine

ObjectivesStreptococcus mutans (S. mutans) is the main aetiologic bacterium of dental caries, whose protein antigen (PAc) has been administered as an anti-caries vaccine. In addition, several fusion proteins or PAc combined with adjuvants were used as anti-caries vaccines to improve the relatively weak immunogenicity of PAc. However, there are no nanoparticle-based adjuvants with good biocompatibility, excellent biodegradability, or the high loading performance of antigens used for anti-caries vaccines. This study aimed to prepare an innovative nanoparticle-based anti-caries vaccine and evaluate immune responses elicited by this vaccine in vitro and in vivo. MethodsIn this study, an anti-caries vaccine was prepared by an antigen of recombinant protein PAc from S. mutans and an adjuvant of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) synthesized using a hydrothermal method. Then, mice were administrated intranasally by ZIF-8@PAc vaccine, and immune responses were evaluated. ResultsZIF-8 NPs not only greatly improved the internalization of the antigen but also released the PAc protein after degradation of ZIF-8 NPs in lysosomes for the further processing and presentation of antigen-presenting cells. In addition, ZIF-8@PAc induced significantly more potent PAc-specific serum IgG and saliva IgA antibodies, a higher splenocyte proliferation index, higher levels of the cytokines IL-4, IL-6, IL-10, IL-17A and IFN-γ, and a higher percentage of mature DCs and CD4+ memory T cells in vivo. ConclusionsThe ZIF-8 NPs, as an anti-caries vaccine adjuvant-assisted antigen PAc, elicit significantly potent immune responses, aiding in the further prevention of dental caries. Clinical significanceVaccine immunotherapy is an attractive strategy for prevention and treatment of dental caries. The ZIF-8@PAc vaccine can induce significantly high level of immune responses in this study, which indicates great potential for prevention and treatment of caries.

De novo design of anti-variant COVID-19 vaccine.

Recent studies highlight the effectiveness of hybrid Severe Acute RespiratorySyndrome-Coronavirus-2 (SARS-CoV-2) vaccines combining wild-type nucleocapsid and Spike proteins. We have further enhanced this strategy by incorporating delta and omicron variants' spike protein mutations. Both delta and omicron mark the shifts in viral transmissibility and severity in unvaccinated and vaccinated patients. So their mutations are highly crucial for future viral variants also. Omicron is particularly adept at immune evasion by mutating spike epitopes. The rapid adaptations of Omicron and sub-variants to spike-based vaccines and simultaneous transmissibility underline the urgency for new vaccines in the continuous battle against SARS-CoV-2. Therefore, we have added three persistent T-cell-stimulating nucleocapsid peptides similar to homologous sequences from seasonal Human Coronaviruses (HuCoV) and an envelope peptide that elicits a strong T-cell immune response. These peptides are clustered in the hybrid spike's cytoplasmic region with non-immunogenic linkers, enabling systematic arrangement. AlphaFold (Artificial intelligence-based model building) analysis suggests omitting the transmembrane domain enhances these cytoplasmic epitopes' folding efficiency which can ensure persistent immunity for CD4+ structural epitopes. Further molecular dynamics simulations validate the compact conformation of the modeled structures and a flexible C-terminus region. Overall, the structures show stability and less conformational fluctuation throughout the simulation. Also, the AlphaFold predicted structural epitopes maintained their folds during simulation to ensure the specificity of CD4+ T-cell response after vaccination. Our proposed approach may provide options for incorporating diverse anti-viral T-cell peptides, similar to HuCoV, into linker regions. This versatility can be promising to address outbreaks and challenges posed by various viruses for effective management in this era of innovative vaccines.

INTRODUCTION: Promoting Drug and Vaccine Innovation and Managing High Prices: Introducing a Special Symposium.

This special JLME symposium addresses ways that federal policy can incentivize innovation in medical therapeutics and make pharmaceuticals more financially accessible.

Exploring the performance of Escherichia coli outer membrane vesicles as a tool for vaccine development against Chagas disease.

Vaccine development is a laborious craftwork in which at least two main components must be defined: a highly immunogenic antigen and a suitable delivery method. Hence, the interplay of these elements could elicit the required immune response to cope with the targeted pathogen with a long-lasting protective capacity. Here we evaluate the properties of Escherichia coli spherical proteoliposomes - known as outer membrane vesicles (OMVs) - as particles with natural adjuvant capacities and as antigen-carrier structures to assemble an innovative prophylactic vaccine for Chagas disease. To achieve this, genetic manipulation was carried out on E. coli using an engineered plasmid containing the Tc24 Trypanosoma cruzi antigen. The goal was to induce the release of OMVs displaying the parasite protein on their surface. As a proof of principle, we observed that native OMVs - as well as those carrying the T. cruzi antigen - were able to trigger a slight, but functional humoral response at low immunization doses. Of note, compared to the non-immunized group, native OMVs-vaccinated animals survived the lethal challenge and showed minor parasitemia values, suggesting a possible involvement of innate trained immunity mechanism. These results open the range for further research on the design of new carrier strategies focused on innate immunity activation as an additional immunization target and venture to seek for alternative forms in which OMVs could be used for optimizing vaccine development.

Evaluation of immunogenicity and efficacy of the enterobactin conjugate vaccine in protecting chickens from colibacillosis.

Colibacillosis is one of the most common and economically devastating infectious diseases in poultry production worldwide. Innovative universal vaccines are urgently needed to protect chickens from the infections caused by genetically diverse avian pathogenic Escherichia coli (APEC). Enterobactin (Ent) is a highly conserved siderophore required for E. coli iron acquisition and pathogenesis. The Ent-specific antibodies induced by a novel Ent conjugate vaccine significantly inhibited the in vitro growth of diverse APEC strains. In this study, White Leghorn chickens were immunized with the Ent conjugate vaccine using a crossed design with two variables, vaccination (with or without) and APEC challenge (O1, O78, or PBS control), resulting in six study groups (9 to 10 birds/group). The chickens were subcutaneously injected with the vaccine (100μg per bird) at 7days of age, followed by booster immunization at 21days of age. The chickens were intratracheally challenged with an APEC strain (108 CFU/bird) or PBS at 28days of age. At 5days post infection, all chickens were euthanized to examine lesions and APEC colonization of the major organs. Immunization of chickens with the Ent vaccine elicited a strong immune response with a 64-fold increase in the level of Ent-specific IgY in serum. The hypervirulent strain O78 caused extensive lesions in lung, air sac, heart, liver, and spleen with significantly reduced lesion scores observed in the vaccinated chickens. Interestingly, the vaccination did not significantly reduce APEC levels in the examined organs. The APEC O1 with low virulence only caused sporadic lesions in the organs in both vaccination and control groups. The Ent conjugate vaccine altered the bacterial community of the ileum and cecum. Taken together, the findings from this study showed the Ent conjugate vaccine could trigger a strong specific immune response and was promising to confer protection against APEC infection.

Computational Prediction of Trypanosoma cruzi Epitopes Toward the Generation of an Epitope-Based Vaccine Against Chagas Disease.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is considered a Neglected Tropical Disease. Limited investment is assigned to its study and control, even though it is one of the most prevalent parasitic infections worldwide. An innovative vaccination strategy involving an epitope-based vaccine that displays multiple immune determinants originating from different antigens could counteract the high biological complexity of the parasite and lead to a wide and protective immune response. In this chapter, we describe a computational reverse vaccinology pipeline applied to identify the most promising peptide sequences from T. cruzi proteins, prioritizing evolutionary conserved sequences, to finally select a list of T and B cell epitope candidates to be further tested in an experimental setting.

Advances in vaccinology and new vaccine platforms

Vaccination stands as one of the most significant advancements in modern medicine. New vaccine platforms, such as mRNA vaccines and viral vector vaccines, have transformed vaccine development, enabling faster responses to emerging threats such as the COVID-19 pandemic. This study aims to improve understanding of the current status of vaccination and its implications for global health by synthesizing the most recent research findings and views from experts in the area. This review covers a wide range of subjects, including advances in vaccine design, delivery technologies, adjuvants, and immunization techniques. This study discusses a variety of topics, including vaccine development methodologies, innovative vaccine platforms, vaccine deployment problems, and future research directions. This assessment highlights the urgent need to accelerate the development and distribution of vaccinations to prevent infectious illnesses.

Calculating Private and Social Returns to COVID-19 Vaccine Innovation

Calculating Private and Social Returns to COVID-19 Vaccine Innovation

Pharmaceutical Innovation in Latin America and the Caribbean.

This study assesses Latin America and Caribbean countries' capacity to innovate new pharmaceuticals, defined as developing new drugs and vaccines, repurposing existing drugs, and inventing around patents to produce new drug variations. Vaccine innovation includes reengineering existing vaccines, developing new manufacturing methods, and the clinical development of unapproved vaccine candidates initiated elsewhere.

Accelerating Vaccine Innovation for Emerging Infectious Diseases via Parallel Discovery

Accelerating Vaccine Innovation for Emerging Infectious Diseases via Parallel Discovery

Accelerating Vaccine Innovation for Emerging Infectious Diseases via Parallel Discovery

The COVID-19 pandemic has raised awareness about the global imperative to develop and stockpile vaccines against future outbreaks of emerging infectious diseases (EIDs). Prior to the pandemic, vaccine development for EIDs was stagnant, largely due to the lack of financial incentives for pharmaceutical firms to invest in vaccine research and development (R&D). This R&D requires significant capital investment, most notably in conducting clinical trials, but vaccines generate much less profit for pharmaceutical firms compared with other therapeutics in disease areas such as oncology. The portfolio approach of financing drug development has been proposed as a financial innovation to improve the risk/return trade-off of investment in drug development projects through the use of diversification and securitization. By investing in a sizable and well-diversified portfolio of novel drug candidates, and issuing equity and securitized debt based on this portfolio, the financial performance of such a biomedical “megafund” can attract a wider group of private-sector investors. To analyze the viability of the portfolio approach in expediting vaccine development against EIDs, we simulate the financial performance of a hypothetical vaccine megafund consisting of 120 messenger RNA (mRNA) vaccine candidates in the preclinical stage, which target 11 EIDs, including a hypothetical “disease X” that may be responsible for the next pandemic. We calibrate the simulation parameters with input from domain experts in mRNA technology and an extensive literature review and find that this vaccine portfolio will generate an average annualized return on investment of −6.0% per annum and a negative net present value of −$9.5 billion, despite the scientific advantages of mRNA technology and the financial benefits of diversification. We also show that clinical trial costs account for 94% of the total investment; vaccine manufacturing costs account for only 6%. The most important factor of the megafund’s financial performance is the price per vaccine dose. Other factors, such as the increased probability of success due to mRNA technology, the size of the megafund portfolio, and the possibility of conducting human challenge trials, do not significantly improve its financial performance. Our analysis indicates that continued collaboration between government agencies and the private sector will be necessary if the goal is to create a sustainable business model and robust vaccine ecosystem for addressing future pandemics.

The Trimeric Artesunate Analog TF27, a Broadly Acting Anti-Infective Model Drug, Exerts Pronounced Anti-SARS-CoV-2 Activity Spanning Variants and Host Cell Types

Starting in 2019, the spread of respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated pandemic of the corona virus disease (COVID-19) has led to enormous efforts in the development of medical countermeasures. Although innovative vaccines have scaled back the number of severe COVID cases, the emergence of the omicron variant (B.1.1.529) illustrates how vaccine development struggles to keep pace with viral evolution. On the other hand, while the recently approved antiviral drugs remdesivir, molnupiravir, and Paxlovid are considered as broadly acting anti-coronavirus therapeutics, only molnupiravir and Paxlovid are orally available and none of these drugs are recommended for prophylactic use. Thus, so far unexploited small molecules, targeting strategies, and antiviral mechanisms are urgently needed to address issues in the current pandemic and in putative future outbreaks of newly emerging variants of concern. Recently, we and others have described the anti-infective potential and particularly the pronounced antiviral activity of artesunate and related compounds of the trioxane/sesquiterpene class. In particular, the trimeric derivative TF27 demonstrated strong anti-cytomegalovirus activity at nanomolar concentrations in vitro as well as in vivo efficacy after oral administration in therapeutic and even prophylactic treatment settings. Here, we extended this analysis by evaluating TF27 for its anti-SARS-CoV-2 potential. Our main findings are as follows: (i) compound TF27 exerted strong anti-SARS-CoV-2 activity in vitro (EC50 = 0.46 ± 0.20 µM), (ii) antiviral activity was clearly distinct from the induction of cytotoxicity, (iii) pretreatment with TF27 prevented virus replication in cultured cells, (iv) antiviral activity has likewise been demonstrated in Calu-3 human lung and Caco-2 human colon cells infected with wild-type, delta, or omicron SARS-CoV-2, respectively, and (v) analysis of TF27 combination treatments has revealed synergistic interaction with GC376, but antagonistic interaction with EIDD-1931. Combined, the data demonstrated the pronounced anti-SARS-CoV-2 activity of TF27 and thus highlight the potential of trioxane compounds for further pharmacologic development towards improved options for COVID-specific medication.

The race toward a universal influenza vaccine: Front runners and the future directions

Influenza virus is the pathogen of influenza (flu) and millions of people suffer from the infection worldwide, posing a significant health risk. The current influenza vaccines induce neutralizing antibodies against hemagglutinin (HA) to achieve strain-specific neutralization. The effectiveness of seasonal vaccines is usually low and unpredictable because of the antigenic variation and genetic plasticity of viruses, as well as the interference of preexisting immunity. A universal influenza vaccine is urgently needed to prevent a wide variety of influenza viruses. Nevertheless, reaching this difficult optimal goal requires a step-by-step approach. Innovative strategies and vaccine platforms are being developed in order to generate robust cross-protective immunity. In this review, we summarize candidate influenza vaccines that meet two criteria: first, they are designed to provide protection against multiple influenza viruses; second, they had passed regulatory evaluations and have entered various stages of clinical trials. We discuss these vaccine candidates based on the different vaccine-production platforms, with the focus on antigen selection, design, adjuvants, immunomodulators, and routes of vaccine delivery in the development of universal influenza vaccines.

Investigating confounding in network-based test-negative design influenza vaccine effectiveness studies-Experience from the DRIVE project.

Establishing a large study network to conduct influenza vaccine effectiveness (IVE) studies while collecting appropriate variables to account for potential bias is important; the most relevant variables should be prioritized. We explored the impact of potential confounders on IVE in the DRIVE multi-country network of sites conducting test-negative design (TND) studies. We constructed a directed acyclic graph (DAG) to map the relationship between influenza vaccination, medically attended influenza infection, confounders, and other variables. Additionally, we used the Development of Robust and Innovative Vaccines Effectiveness (DRIVE) data from the 2018/2019 and 2019/2020 seasons to explore the effect of covariate adjustment on IVE estimates. The reference model was adjusted for age, sex, calendar time, and season. The covariates studied were presence of at least one, two, or three chronic diseases; presence of six specific chronic diseases; and prior healthcare use. Analyses were conducted by site and subsequently pooled. The following variables were included in the DAG: age, sex, time within influenza season and year, health status and comorbidities, study site, health-care-seeking behavior, contact patterns and social precautionary behavior, socioeconomic status, and pre-existing immunity. Across all age groups and settings, only adjustment for lung disease in older adults in the primary care setting resulted in a relative change of the IVE point estimate >10%. Our study supports a parsimonious approach to confounder adjustment in TND studies, limited to adjusting for age, sex, and calendar time. Practical implications are that necessitating fewer variables lowers the threshold for enrollment of sites in IVE studies and simplifies the pooling of data from different IVE studies or study networks.

Ranking of immunization programs in Latin America, 2019Ranking dos programas de imunização na América Latina, 2019

To establish a ranking of national immunization programs in Latin America that compares the various realities, identifies challenges and unachieved goals, and encourages countries to search for strategies to overcome the obstacles they face. Ten countries with the most innovative national vaccination schedules (NVCs) were selected. Information published on official websites of ministries of health, the World Health Organization (WHO), the Pan American Health Organization (PAHO), and the United Nations Children's Fund (UNICEF) were used, as well as interviews with experts from each country. A ranking was constructed, based on domains linked to the 2019 NVC (vaccinations given at different life stages, influenza vaccination, and vaccination in special situations); vaccination coverage in 2018; and programmatic aspects. The general ranking is led by Chile and Panama, due to vaccination in the first and second year of life. They are followed by Argentina, Uruguay, and Costa Rica, which stand out for vaccination of other groups, influenza vaccination, and programmatic aspects. Brazil, Colombia, and Mexico have more delays in their NVCs, as well as programmatic gaps and lower vaccination coverages. Finally, Paraguay and Peru have similar deficiencies and bigger information gaps. However, when the domains are analyzed individually, the ranking changes and the same pattern is not repeated. This is the first ranking of national immunization programs in Latin America that highlights strengths and weaknesses in each country. The periodicity of this exercise will be key when comparing the evolution and positioning of these programs over time.