Vaccination Strategies
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2021 ◽  
Laura Sandra Lello ◽  
Koen Bartholomeeusen ◽  
Sainan Wang ◽  
Sandra Coppens ◽  
Rennos Fragkoudis ◽  

Alphaviruses have positive-strand RNA genomes containing two open reading frames (ORFs). The first ORF encodes the non-structural (ns) polyproteins P123 and P1234 that act as precursors for the subunits of the viral RNA replicase (nsP1-nsP4). Processing of P1234 leads to the formation of a negative-strand replicase consisting of nsP4 (RNA polymerase) and P123 components. Subsequent processing of P123 results in a positive-strand replicase. The second ORF encoding the structural proteins is expressed via the synthesis of a subgenomic RNA. Alphavirus replicase is capable of using template RNAs that contain essential cis -active sequences. Here we demonstrate that the replicases of nine alphaviruses, expressed in the form of separate P123 and nsP4 components, are active. Their activity depends on the abundance of nsP4. The match of nsP4 to its template strongly influences efficient subgenomic RNA synthesis. nsP4 of Barmah Forest virus (BFV) formed a functional replicase only with matching P123 while nsP4s of other alphaviruses were compatible also with several heterologous P123s. The P123 components of Venezuelan equine encephalitis virus and Sindbis virus (SINV) required matching nsP4s while P123 of other viruses could form active replicases with different nsP4s. Chimeras of Semliki Forest virus, harboring the nsP4 of chikungunya virus, Ross River virus, BFV or SINV were viable. In contrast, chimeras of SINV, harboring an nsP4 from different alphaviruses, exhibited a temperature-sensitive phenotype. These findings highlight the possibility for formation of new alphaviruses via recombination events and provide a novel approach for the development of attenuated chimeric viruses for vaccination strategies. Importance. A key element of every virus with an RNA genome is the RNA replicase. Understanding the principles of RNA replicase formation and functioning is therefore crucial for understanding and responding to the emergence of new viruses. Reconstruction of the replicases of nine alphaviruses from nsP4 and P123 polyproteins revealed that the nsP4 of the majority of alphaviruses, including the mosquito-specific Eilat virus, could form a functional replicase with P123 originating from a different virus, and the corresponding chimeric viruses were replication-competent. nsP4 also had an evident role in determining the template RNA preference and the efficiency of RNA synthesis. The revealed broad picture of the compatibility of the replicase components of alphaviruses is important for understanding the formation and functioning of the alphavirus RNA replicase and highlights the possibilities for recombination between different alphavirus species.

Bruce Mellado ◽  
Jianhong Wu ◽  
Jude Dzevela Kong ◽  
Nicola Luigi Bragazzi ◽  
Ali Asgary ◽  

COVID-19 is imposing massive health, social and economic costs. While many developed countries have started vaccinating, most African nations are waiting for vaccine stocks to be allocated and are using clinical public health (CPH) strategies to control the pandemic. The emergence of variants of concern (VOC), unequal access to the vaccine supply and locally specific logistical and vaccine delivery parameters, add complexity to national CPH strategies and amplify the urgent need for effective CPH policies. Big data and artificial intelligence machine learning techniques and collaborations can be instrumental in an accurate, timely, locally nuanced analysis of multiple data sources to inform CPH decision-making, vaccination strategies and their staged roll-out. The Africa-Canada Artificial Intelligence and Data Innovation Consortium (ACADIC) has been established to develop and employ machine learning techniques to design CPH strategies in Africa, which requires ongoing collaboration, testing and development to maximize the equity and effectiveness of COVID-19-related CPH interventions.

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255063
Brian E. Dixon ◽  
Shaun J. Grannis ◽  
Lauren R. Lembcke ◽  
Nimish Valvi ◽  
Anna R. Roberts ◽  

Background Early studies on COVID-19 identified unequal patterns in hospitalization and mortality in urban environments for racial and ethnic minorities. These studies were primarily single center observational studies conducted within the first few weeks or months of the pandemic. We sought to examine trends in COVID-19 morbidity, hospitalization, and mortality over time for minority and rural populations, especially during the U.S. fall surge. Methods Data were extracted from a statewide cohort of all adult residents in Indiana tested for SARS-CoV-2 infection between March 1 and December 31, 2020, linked to electronic health records. Primary measures were per capita rates of infection, hospitalization, and death. Age adjusted rates were calculated for multiple time periods corresponding to public health mitigation efforts. Comparisons across time within groups were compared using ANOVA. Results Morbidity and mortality increased over time with notable differences among sub-populations. Initially, hospitalization rates among racial minorities were 3–4 times higher than whites, and mortality rates among urban residents were twice those of rural residents. By fall 2020, hospitalization and mortality rates in rural areas surpassed those of urban areas, and gaps between black/brown and white populations narrowed. Changes across time among demographic groups was significant for morbidity and hospitalization. Cumulative morbidity and mortality were highest among minority groups and in rural communities. Conclusions The synchronicity of disparities in COVID-19 by race and geography suggests that health officials should explicitly measure disparities and adjust mitigation as well as vaccination strategies to protect those sub-populations with greater disease burden.

2021 ◽  
Vol 118 (30) ◽  
pp. e2100576118
Patricia Avancena ◽  
Tengfei Song ◽  
Yonghong Yao ◽  
Hannah Fehlner-Peach ◽  
Betty Diamond ◽  

Antibody affinity maturation occurs in the germinal center (GC), a highly dynamic structure that arises upon antigen stimulation and recedes after infection is resolved. While the magnitude of the GC reaction is highly fluctuating and depends on antigens or pathological conditions, it is unclear whether GCs are assembled ad hoc in different locations or in preexisting niches within B cell follicles. We show that follicular dendritic cells (FDCs), the essential cellular components of the GC architecture, form a predetermined number of clusters. The total number of FDC clusters is the same on several different genetic backgrounds and is not altered by immunization or inflammatory conditions. In unimmunized and germ-free mice, a few FDC clusters contain GC B cells; in contrast, immunization or autoimmune milieu significantly increases the frequency of FDC clusters occupied by GC B cells. Excessive occupancy of GC niches by GC B cells after repeated immunizations or in autoimmune conditions suppresses subsequent antibody responses to new antigens. These data indicate that the magnitude of the GC reaction is restricted by a fixed number of permissive GC niches containing preassembled FDC clusters. This finding may help in the future design of vaccination strategies and in the modulation of antibody-mediated autoimmunity.

2021 ◽  
Vol 42 (1 Supl) ◽  
pp. 35
Marcelo Domingos Marchesin ◽  
Mehran Sabeti

In this work we analyze the effectiveness of vaccination strategies for the COVID-19 epidemic in the Brazilian state of Minas Gerais. Firstly we study the effectiveness of general vaccination in the decreasing of the number of infected individuals using a traditional non structured SEIR model. Secondly we consider an age-structured SEIR model with three age classes (youngster, adult and elderly) and we analyze the current strategy in the Brazilian state of Minas Gerais, of focusing the vaccination on the elderly group. We conclude by showing this strategy to be mistaken and that a vaccination focusing on the age group of the adults would be much more efficient in decreasing the total number of infected individuals.

Epidemiologia ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 271-293
Gilberto Gonzalez-Parra

The first round of vaccination against coronavirus disease 2019 (COVID-19) began in early December of 2020 in a few countries. There are several vaccines, and each has a different efficacy and mechanism of action. Several countries, for example, the United Kingdom and the USA, have been able to develop consistent vaccination programs where a great percentage of the population has been vaccinated (May 2021). However, in other countries, a low percentage of the population has been vaccinated due to constraints related to vaccine supply and distribution capacity. Countries such as the USA and the UK have implemented different vaccination strategies, and some scholars have been debating the optimal strategy for vaccine campaigns. This problem is complex due to the great number of variables that affect the relevant outcomes. In this article, we study the impact of different vaccination regimens on main health outcomes such as deaths, hospitalizations, and the number of infected. We develop a mathematical model of COVID-19 transmission to focus on this important health policy issue. Thus, we are able to identify the optimal strategy regarding vaccination campaigns. We find that for vaccines with high efficacy (>70%) after the first dose, the optimal strategy is to delay inoculation with the second dose. On the other hand, for a low first dose vaccine efficacy, it is better to use the standard vaccination regimen of 4 weeks between doses. Thus, under the delayed second dose option, a campaign focus on generating a certain immunity in as great a number of people as fast as possible is preferable to having an almost perfect immunity in fewer people first. Therefore, based on these results, we suggest that the UK implemented a better vaccination campaign than that in the USA with regard to time between doses. The results presented here provide scientific guidelines for other countries where vaccination campaigns are just starting, or the percentage of vaccinated people is small.

2021 ◽  
Vol 6 ◽  
pp. 185
Natsuko Imai ◽  
Alexandra B. Hogan ◽  
Lucy Williams ◽  
Anne Cori ◽  
Tara D. Mangal ◽  

Background: The multiple efficacious vaccines authorised for emergency use worldwide represent the first preventative intervention against coronavirus disease 2019 (COVID-19) that does not rely on social distancing measures. The speed at which data are emerging and the heterogeneities in study design, target populations, and implementation make it challenging to interpret and assess the likely impact of vaccine campaigns on local epidemics. We reviewed available vaccine efficacy and effectiveness studies to generate working estimates that can be used to parameterise simulation studies of vaccine impact. Methods: We searched MEDLINE, the World Health Organization’s Institutional Repository for Information Sharing, medRxiv, and vaccine manufacturer websites for studies that evaluated the emerging data on COVID-19 vaccine efficacy and effectiveness. Studies providing an estimate of the efficacy or effectiveness of a COVID-19 vaccine using disaggregated data against SARS-CoV-2 infection, symptomatic disease, severe disease, death, or transmission were included. We extracted information on study population, variants of concern (VOC), vaccine platform, dose schedule, study endpoints, and measures of impact. We applied an evidence synthesis approach to capture a range of plausible and consistent parameters for vaccine efficacy and effectiveness that can be used to inform and explore a variety of vaccination strategies as the COVID-19 pandemic evolves. Results: Of the 602 articles and reports identified, 53 were included in the analysis. The availability of vaccine efficacy and effectiveness estimates varied by vaccine and were limited for VOCs. Estimates for non-primary endpoints such as effectiveness against infection and onward transmission were sparse. Synthesised estimates were relatively consistent for the same vaccine platform for wild-type, but was more variable for VOCs. Conclusions: Assessment of efficacy and effectiveness of COVID-19 vaccines is complex. Simulation studies must acknowledge and capture the uncertainty in vaccine effectiveness to robustly explore and inform vaccination policies and policy around the lifting of non-pharmaceutical interventions.

2021 ◽  
Julie Collins ◽  
Rosie Westerveld ◽  
Kate A Nelson ◽  
Hana Rohan ◽  
Hilary Bower ◽  

Introduction: COVID-19 vaccines are now being distributed to low- and middle-income countries (LMICs), with global urgency surrounding national vaccination plans. LMICs have significant experience implementing vaccination campaigns to respond to epidemic threats but are often hindered by chronic health system challenges. We sought to identify transferable lessons for COVID-19 vaccination from the rollout of three vaccines that targeted adult groups in Africa and South America: MenAfriVac (meningitis A); 17D (yellow fever); and rVSV-ZEBOV (Ebola virus disease). Methods: We conducted a rapid literature review and 24 semi-structured interviews with technical experts who had direct implementation experience with the selected vaccines in Africa and South America. We identified barriers, enablers, and key lessons from the literature and from participants&#39 experiences. Interview data were analysed thematically according to seven implementation domains. Results: Participants highlighted multiple components of vaccination campaigns that are instrumental for achieving high coverage. Community engagement is an essential and effective tool, requiring dedicated time, funding and workforce. Involving local health workers is a key enabler, as is collaborating with community leaders to map social groups and tailor vaccination strategies to their needs. Vaccination team recruitment and training strategies need to be enhanced to support vaccination campaigns. Although recognised as challenging, integrating vaccination campaigns with other routine health services can be highly beneficial if well planned and coordinated across health programmes and with communities. Conclusion: As supplies of COVID-19 vaccines become available to LMICs, countries need to prepare to efficiently roll out the vaccine, encourage uptake among eligible groups, and respond to potential community concerns. Lessons from the implementation of these three vaccines that targeted adults in LMICs can be used to inform best practice for COVID-19 and other epidemic vaccination campaigns.

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254430
Mario Moisés Alvarez ◽  
Sergio Bravo-González ◽  
Grissel Trujillo-de Santiago

We have investigated the importance of the rate of vaccination to contain COVID-19 in urban areas. We used an extremely simple epidemiological model that is amenable to implementation in an Excel spreadsheet and includes the demographics of social distancing, efficacy of massive testing and quarantine, and coverage and rate of vaccination as the main parameters to model the progression of COVID-19 pandemics in densely populated urban areas. Our model predicts that effective containment of pandemic progression in densely populated cities would be more effectively achieved by vaccination campaigns that consider the fast distribution and application of vaccines (i.e., 50% coverage in 6 months) while social distancing measures are still in place. Our results suggest that the rate of vaccination is more important than the overall vaccination coverage for containing COVID-19. In addition, our modeling indicates that widespread testing and quarantining of infected subjects would greatly benefit the success of vaccination campaigns. We envision this simple model as a friendly, readily accessible, and cost-effective tool for assisting health officials and local governments in the rational design/planning of vaccination strategies.

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1392
Elene A. Clemens ◽  
Martha A. Alexander-Miller

The immune system of young infants is both quantitatively and qualitatively distinct from that of adults, with diminished responsiveness leaving these individuals vulnerable to infection. Because of this, young infants suffer increased morbidity and mortality from respiratory pathogens such as influenza viruses. The impaired generation of robust and persistent antibody responses in these individuals makes overcoming this increased vulnerability through vaccination challenging. Because of this, an effective vaccine against influenza viruses in infants under 6 months is not available. Furthermore, vaccination against influenza viruses is challenging even in adults due to the high antigenic variability across viral strains, allowing immune evasion even after induction of robust immune responses. This has led to substantial interest in understanding how specific antibody responses are formed to variable and conserved components of influenza viruses, as immune responses tend to strongly favor recognition of variable epitopes. Elicitation of broadly protective antibody in young infants, therefore, requires that both the unique characteristics of young infant immunity as well as the antibody immunodominance present among epitopes be effectively addressed. Here, we review our current understanding of the antibody response in newborns and young infants and discuss recent developments in vaccination strategies that can modulate both magnitude and epitope specificity of IAV-specific antibody.

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