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INTRODUCTION: The COVID-19 pandemic catalyzed unprecedented vaccine innovation, revealing critical shortcomings in achieving equitable vaccine access and underscoring the need for a focused review of the lessons learned to inform future pandemic preparedness, with emphasis on vaccine delivery, equity, and challenges in LMICs. AREAS COVERED: We critically analyzed the pandemic vaccine development and distribution journey and the operational mechanisms that facilitated these achievements. For this purpose, we primarily searched pandemic vaccine stakeholder websites, reports, and publications. The analysis extends beyond the scientific narrative to address the 'how' of the process while anchoring the discussion on equity and global health security as fundamental to preparing for future pandemics. EXPERT OPINION: Drawing on the insights gained from the COVID-19 pandemic, we identify several key challenges requiring immediate attention to fortify preparedness for future pandemics. These are cultivating leadership in the field of vaccinology, guaranteeing equitable global access to diagnostics, therapeutic agents, and vaccines, securing adequate funding for ongoing research and development, ensuring the fair distribution of vaccines, and strategically allocating biomedical manufacturing facilities to ensure a balanced global production capacity. Addressing these challenges is imperative to establish a robust pandemic response framework and mitigate the impact of future global health crises.
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COVID-19 Vaccines , COVID-19 , Global Health , Pandemics , Vaccine Development , Humans , COVID-19/prevention & control , COVID-19/epidemiology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Pandemics/prevention & control , Developing Countries , SARS-CoV-2/immunology , Pandemic PreparednessABSTRACT
Non-typhoidal Salmonella (NTS) infection and invasive non-typhoidal Salmonella (iNTS) infection cause a significant global health and economic burden. This systematic review aims to investigate the reported economic burden of NTS and iNTS infection, identify research gaps, and suggest future research directions. Data from PubMed and Embase databases up to April 2022 were reviewed, and articles were screened based on predefined criteria. Cost data were extracted, categorized into direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs), and converted into US dollars (year 2022). Data primarily originated from high-income countries (37 out of 38), with limited representation from Africa and resource-limited settings. For inpatients, DMCs were the primary cost driver for both NTS and iNTS illnesses, with estimates ranging from USD 545.9 (Taiwan, a region of China) to USD 21,179.8 (Türkiye) for NTS and from USD 1973.1 (Taiwan, a region of China) to USD 32,507.5 (United States of America) for iNTS per case. DNMCs and ICs varied widely across studies. Although study quality improved over time, methodological differences persisted. This review underscores the lack of economic data on NTS and iNTS in resource-limited settings. It also highlights the need for economic burden data in resource-limited settings and a standardized approach to generate global datasets, which is critical for informing policy decisions, especially regarding future vaccines.
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BACKGROUND: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year. METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters). RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds. CONCLUSION: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity. CLINICAL TRIALS REGISTRATION: NCT05109559.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Adult , Female , Humans , Male , Middle Aged , Young Adult , Ad26COVS1/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Coronavirus Nucleocapsid Proteins/immunology , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Follow-Up Studies , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interferon-gamma/immunology , Phosphoproteins/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Thailand , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosageABSTRACT
For vaccine development and adoption decisions, the 'Full Value of Vaccine Assessment' (FVVA) framework has been proposed by the WHO to expand the range of evidence available to support the prioritization of candidate vaccines for investment and eventual uptake by low- and middle-income countries. Recent applications of the FVVA framework have already shown benefits. Building on the success of these applications, we see important new opportunities to maximize the future utility of FVVAs to country and global stakeholders and provide a proof-of-concept for analyses in other areas of disease control and prevention. These opportunities include the following: (1) FVVA producers should aim to create evidence that explicitly meets the needs of multiple key FVVA consumers, (2) the WHO and other key stakeholders should develop standardized methodologies for FVVAs, as well as guidance for how different stakeholders can explicitly reflect their values within the FVVA framework, and (3) the WHO should convene experts to further develop and prioritize the research agenda for outcomes and benefits relevant to the FVVA and elucidate methodological approaches and opportunities for standardization not only for less well-established benefits, but also for any relevant research gaps. We encourage FVVA stakeholders to engage with these opportunities.
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We compared high-risk human papillomavirus (HPV) detection on first-stream urine from self-sampled collection device (Colli-Pee) and same-day clinician-collected cervical swab in 240 women. Testing with automated cobas 4800 system showed 96.7 % concordance (198 concordant-negative, 34 concordant-positive, Cohen's kappa=0.87). HPV testing on Colli-Pee urine offers advantages for acceptable non-invasive HPV screening.
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Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Real-Time Polymerase Chain Reaction , Papillomavirus Infections/diagnosis , Sensitivity and Specificity , Papillomaviridae/genetics , DNA, Viral/genetics , DNA, Viral/analysis , Uterine Cervical Neoplasms/diagnosis , Early Detection of Cancer , Uterine Cervical Dysplasia/diagnosisABSTRACT
The spectrum of diseases caused by Streptococcus pyogenes (Strep A) ranges from superficial to serious life-threatening invasive infections. We conducted a scoping review of published articles between 1980 and 2021 to synthesize evidence of state transitions across the Strep A disease spectrum. We identified 175 articles reporting 262 distinct observations of Strep A disease state transitions. Among the included articles, the transition from an invasive or toxin-mediated disease state to another disease state (i.e., to recurrent ARF, RHD or death) was described 115 times (43.9% of all included transition pairs) while the transition to and from locally invasive category was the lowest (n = 7; 0.02%). Transitions from well to any other state was most frequently reported (49%) whereas a relatively higher number of studies (n = 71) reported transition from invasive disease to death. Transitions from any disease state to locally invasive, Strep A pharyngitis to invasive disease, and chronic kidney disease to death were lacking. Transitions related to severe invasive diseases were more frequently reported than superficial ones. Most evidence originated from high-income countries and there is a critical need for new studies in low- and middle-income countries to infer the state transitions across the Strep A disease spectrum in these high-burden settings.
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Pharyngitis , Rheumatic Fever , Streptococcal Infections , Humans , Streptococcus pyogenes , Evidence Gaps , Streptococcal Infections/epidemiologyABSTRACT
Climate change represents an unprecedented threat to humanity and will be the ultimate challenge of the 21st century. As a public health consequence, the World Health Organization estimates an additional 250,000 deaths annually by 2030, with resource-poor countries being predominantly affected. Although climate change's direct and indirect consequences on human health are manifold and far from fully explored, a growing body of evidence demonstrates its potential to exacerbate the frequency and spread of transmissible infectious diseases. Effective, high-impact mitigation measures are critical in combating this global crisis. While vaccines and vaccination are among the most cost-effective public health interventions, they have yet to be established as a major strategy in climate change-related health effect mitigation. In this narrative review, we synthesize the available evidence on the effect of climate change on vaccine-preventable diseases. This review examines the direct effect of climate change on water-related diseases such as cholera and other enteropathogens, helminthic infections and leptospirosis. It also explores the effects of rising temperatures on vector-borne diseases like dengue, chikungunya, and malaria, as well as the impact of temperature and humidity on airborne diseases like influenza and respiratory syncytial virus infection. Recent advances in global vaccine development facilitate the use of vaccines and vaccination as a mitigation strategy in the agenda against climate change consequences. A focused evaluation of vaccine research and development, funding, and distribution related to climate change is required.
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Communicable Diseases , Vaccines , Humans , Climate Change , Public Health , VaccinationABSTRACT
Group A Streptococcus causes a wide range of diseases from relatively mild infections including pharyngitis to more severe illnesses such as invasive diseases and rheumatic heart disease (RHD). Our aim is to estimate the cost-effectiveness of a hypothetical Strep A vaccine on multiple disease manifestations at the global-level. Cost-effectiveness analyses were carried out by building on the potential epidemiological impact of vaccines that align with the WHO's Preferred Product Characteristics for Strep A vaccines. Maximum vaccination costs for a cost-effective vaccination strategy were estimated at the thresholds of 1XGDP per capita and health opportunity costs. The maximum cost per fully vaccinated person for Strep A vaccination to be cost-effective was $385-$489 in high-income countries, $213-$312 in upper-income-income countries, $74-$132 in lower-middle-income countries, and $37-$69 in low-income countries for routine vaccination at birth and 5 years of age respectively. While the threshold costs are sensitive to vaccine characteristics such as efficacy, and waning immunity, a cost-effective Strep A vaccine will lower morbidity and mortality burden in all income settings.
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BACKGROUND: Leptospirosis, a prevalent zoonotic disease with One Health priority and a disease of poverty, lacks global economic burden estimates. This study aims to determine the global, regional, and country-level cost of leptospirosis due to loss of productivity. METHODOLOGY/PRINCIPAL FINDINGS: The cost of leptospirosis due to loss of productivity (referred to as productivity cost hereafter) was estimated by converting the disability-adjusted life years (DALYs) lost due to leptospirosis to a monetary value using the per capita gross domestic product (GDP). The country-specific DALYs lost were obtained from the global burden of leptospirosis study published previously. Non-health GDP per capita (GDP- per capita health expenditure) was used for the cost conversion of DALYs. Country-specific GDP and health expenditure data were obtained from the World Bank data repositories. Estimates were done using both nominal and international dollars. The estimated global productivity cost of leptospirosis in 2019 was Int$ 29.3 billion, with low and high estimates ranging from Int$ 11.6 billion to 52.3 billion. China (Int$ 4.8 billion), India (Int$ 4.6 billion), Indonesia (Int$ 2.8 billion), Sri Lanka (Int$ 2.1 billion), and the United States (Int$ 1.3 billion) had the highest productivity cost due to leptospirosis. Eight out of 10 countries with the highest burden were in the Asia-Pacific region. In addition, lower-middle-income countries had an annual productivity cost of Int$ 13.8 billion, indicating that the disease is poverty-related. CONCLUSION: Although significant, the cost estimate due to loss of productivity is merely a fraction of the overall economic burden of this disease, which also includes other direct, indirect, and intangible costs. The existing partial estimates of the different components of economic cost suggest a profound economic burden that demands the inclusion of leptospirosis in the global health agenda for comprehensive disease control and prevention efforts, including vaccine development.
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Leptospirosis , Humans , Animals , Zoonoses , China , Disability-Adjusted Life Years , Sri LankaABSTRACT
Investment in Strep A vaccine R&D is disproportionately low relative to the large burden of Strep A diseases globally. This study presents a novel Strep A vaccine global demand and financial forecast model with estimates of potential global demand and associated revenue and profits for a hypothetical Strep A vaccine as well as a net present value (NPV) analysis of return on capital investments required to develop the vaccine. A positive NPV was calculated for a variety of developer scenarios and target populations, including the global rollout of the vaccine in private and public markets by a multinational pharmaceutical corporation and a staged rollout by a developing country vaccine manufacturer for both infant and child populations. The results suggest there is a viable commercial market for a Strep A vaccine. It is hoped that this study will help to inform industry decision-making and drive increased prioritization of, and investment in, Strep A vaccine research and development.
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BACKGROUND: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented. METHODS: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood. RESULTS: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups. CONCLUSIONS: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups. CLINICAL TRIALS REGISTRATION: NCT05109559.
Subject(s)
COVID-19 , Vaccines , Adult , Humans , COVID-19/prevention & control , SARS-CoV-2 , COVID-19 Vaccines/adverse effects , Ad26COVS1 , Antibodies, Neutralizing , Antibodies, Viral , Immunogenicity, VaccineABSTRACT
Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a 'multiple shots on goal' approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible, vesicular stomatitis virus or adenovirus vectors, messenger RNA (mRNA), whole inactivated virus, nanoparticle and recombinant protein technologies, which led to multiple effective COVID-19 vaccines. The challenge of COVID-19 vaccine inequity, as COVID-19 spread globally, created a situation where cutting-edge mRNA technologies were preferentially supplied by multinational pharmaceutical companies to high-income countries while low and middle-income countries (LMICs) were pushed to the back of the queue and relied more heavily on adenoviral vector, inactivated virus and recombinant protein vaccines. To prevent this from occurring in future pandemics, it is essential to expand the scale-up capacity for both traditional and new vaccine technologies at individual or simultaneous hubs in LMICs. In parallel, a process of tech transfer of new technologies to LMIC producers needs to be facilitated and funded, while building LMIC national regulatory capacity, with the aim of several reaching 'stringent regulator' status. Access to doses is an essential start but is not sufficient, as healthcare infrastructure for vaccination and combating dangerous antivaccine programmes both require support. Finally, there is urgency to establish an international framework through a United Nations Pandemic Treaty to promote, support and harmonise a more robust, coordinated and effective global response.
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COVID-19 , Hemorrhagic Fever, Ebola , Influenza Vaccines , Influenza, Human , Humans , COVID-19 Vaccines , Influenza, Human/epidemiology , Pandemics/prevention & control , COVID-19/prevention & control , Neglected DiseasesABSTRACT
The COVID-19 pandemic triggered a sense of vulnerability and urgency that led to concerted actions by governments, funders, regulators and industry to overcome traditional challenges for the development of vaccine candidates and to reach authorisation. Unprecedented financial investments, massive demand, accelerated clinical development and regulatory reviews were among the key factors that contributed to accelerating the development and approval of COVID-19 vaccines. The rapid development of COVID-19 vaccines benefited of previous scientific innovations such as mRNA and recombinant vectors and proteins. This has created a new era of vaccinology, with powerful platform technologies and a new model for vaccine development. These lessons learnt highlight the need of strong leadership, to bring together governments, global health organisations, manufacturers, scientists, private sector, civil society and philanthropy, to generate innovative, fair and equitable access mechanisms to COVID-19 vaccines for populations worldwide and to build a more efficient and effective vaccine ecosystem to prepare for other pandemics that may emerge. With a longer-term view, new vaccines must be developed with incentives to build expertise for manufacturing that can be leveraged for low/middle-income countries and other markets to ensure equity in innovation, access and delivery. The creation of vaccine manufacturing hubs with appropriate and sustained training, in particular in Africa, is certainly the way of the future to a new public health era to safeguard the health and economic security of the continent and guarantee vaccine security and access, with however the need for such capacity to be sustained in the interpandemic period.
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COVID-19 , Vaccines , Humans , COVID-19 Vaccines , Pandemics/prevention & control , COVID-19/prevention & control , EcosystemABSTRACT
Although significant progress has been made in achieving goals for COVID-19 vaccine access, the quest for equity and justice remains an unfinished agenda. Vaccine nationalism has prompted calls for new approaches to achieve equitable access and justice not only for vaccines but also for vaccination. This includes ensuring country and community participation in global discussions and that local needs to strengthen health systems, address issues related to social determinants of health, build trust and leverage acceptance to vaccines, are addressed. Regional vaccine technology and manufacturing hubs are promising approaches to address access challenges and must be integrated with efforts to ensure demand. The current situation underlines the need for access, demand and system strengthening to be addressed along with local priorities for justice to be achieved. Innovations to improve accountability and leverage existing platforms are also needed. Sustained political will and investment is required to ensure ongoing production of non-pandemic vaccines and sustained demand, particularly when perceived threat of disease appears to be waning. Several recommendations are made to govern towards justice including codesigning the path forward with low-income and middle-income countries; establishing stronger accountability measures; establishing dedicated groups to engage with countries and manufacturing hubs to ensure that the affordable supply and predictable demand are in balance; addressing country needs for health system strengthening through leveraging existing health and development platforms and delivering on product presentations informed by country needs. Even if difficult, we must converge on a definition of justice well in advance of the next pandemic.
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COVID-19 , Vaccines , Humans , COVID-19 Vaccines , COVID-19/prevention & control , Vaccination , Social JusticeABSTRACT
The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6-8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population. Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080.
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AIDS Vaccines , HIV Infections , HIV Seropositivity , HIV-1 , Humans , Antibody Formation , HIV Infections/prevention & control , Immunization, Secondary/methods , Antibody Specificity , HIV Antibodies , HIV Envelope Protein gp120ABSTRACT
Streptococcus pyogenes (Strep A) infections result in a vastly underestimated burden of acute and chronic disease globally. The Strep A Vaccine Global Consortium's (SAVAC's) mission is to accelerate the development of safe, effective, and affordable S. pyogenes vaccines. The safety of vaccine recipients is of paramount importance. A single S. pyogenes vaccine clinical trial conducted in the 1960s raised important safety concerns. A SAVAC Safety Working Group was established to review the safety assessment methodology and results of more recent early-phase clinical trials and to consider future challenges for vaccine safety assessments across all phases of vaccine development. No clinical or biological safety signals were detected in any of these early-phase trials in the modern era. Improvements in vaccine safety assessments need further consideration, particularly for pediatric clinical trials, large-scale efficacy trials, and preparation for post-marketing pharmacovigilance.
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Streptococcal Infections , Streptococcal Vaccines , Child , Humans , Streptococcal Infections/drug therapy , Streptococcus pyogenes , Clinical Trials as TopicABSTRACT
Considering the lack of existing evidence on economic burden for diseases caused by group A Streptococcus, we estimated the economic burden per episode for selected diseases. Each cost component of direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs) was separately extrapolated and aggregated to estimate the economic burden per episode by income group as classified by the World Bank. Adjustment factors for DMC and DNMC were generated to overcome related data insufficiencies. To address uncertainty surrounding input parameters, a probabilistic multivariate sensitivity was carried out. The average economic burden per episode ranged from $22 to $392 for pharyngitis, $25 to $2,903 for impetigo, $47 to $2,725 for cellulitis, $662 to $34,330 for invasive and toxin-mediated infections, $231 to $6,332 for acute rheumatic fever (ARF), $449 to $11,717 for rheumatic heart disease (RHD), and $949 to $39,560 for severe RHD across income groups. The economic burden for multiple Group A Streptococcus diseases underscores an urgent need to develop effective prevention strategies including vaccines.
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Objective: The aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. Methods: Cross-sectional surveys were conducted among grade 10 (15-16 years old) and grade 12 (17-18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-Peeâ device from November 2018 to February 2019. The samples were initially tested using Cobasâ 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by Anyplexâ assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. Results: Prevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. Conclusion: A substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.
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Recent efforts have re-invigorated the Streptococcus pyogenes (Group A Streptococcus) vaccine development field, though scientific, regulatory and commercial barriers persist, and the vaccine pipeline remains sparse. There is an ongoing need to accelerate all aspects of development to address the large global burden of disease caused by the pathogen. Building on over 100 years of S. pyogenes vaccine development, there are currently eight candidates on a product development track, including four M protein-based candidates and four candidates designed around non-M protein antigens. These candidates have demonstrated proof of concept for protection against S. pyogenes in preclinical models, one has demonstrated safety and immunogenicity in a Phase 1 trial and at least four others are poised to soon enter clinical trials. To maintain momentum, the Strep A Vaccine Global Consortium (SAVAC) was established to bring together experts to accelerate global S. pyogenes vaccine development. This article highlights the past, present and future of S. pyogenes vaccine development and emphasizes key priorities, and the role of SAVAC, in advancing the field.
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Understanding immunity in humans to Group A Streptococcus (Strep A) is critical for the development of successful vaccines to prevent the morbidity and mortality attributed to Strep A infections. Despite decades of effort, no licensed vaccine against Strep A exists and immune correlates of protection are lacking; a major impediment to vaccine development. In the absence of a vaccine, we can take cues from the development of natural immunity to Strep A in humans to identify immune correlates of protection. The age stratification of incidence of acute Strep A infections, peaking in young children and waning in early adulthood, coincides with the development of specific immune responses. Therefore, understanding the immune mechanisms involved in natural protection from acute Strep A infection is critical to identifying immune correlates to inform vaccine development. This perspective summarises the findings from natural infection studies, existing assays of immunity to Strep A, and highlights the gaps in knowledge to guide the development of Strep A vaccines and associated correlates of protection.