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1. Vaccine nationalism and the dynamics and control of SARS-CoV-2

   https://doi.org/10.1126/science.abj7364  

   Wagner, Caroline E.; Saad-Roy, Chadi M.; Morris, Sinead E.; Baker, Rachel E.; Mina, Michael J.; Farrar, Jeremy; Holmes, Edward C.; Pybus, Oliver G.; Graham, Andrea L.; Emanuel, Ezekiel J.; et al (August 2021, Science)

   null (Ed.)

   Vaccines provide powerful tools to mitigate the enormous public health and economic costs that the ongoing SARS-CoV-2 pandemic continues to exert globally, yet vaccine distribution remains unequal among countries. To examine the potential epidemiological and evolutionary impacts of ‘vaccine nationalism’, we extend previous models to include simple scenarios of stockpiling between two regions. In general, when vaccines are widely available and the immunity they confer is robust, sharing doses minimizes total cases across regions. A number of subtleties arise when the populations and transmission rates in each region differ, depending on evolutionary assumptions and vaccine availability. When the waning of natural immunity contributes most to evolutionary potential, sustained transmission in low access regions results in an increased potential for antigenic evolution, which may result in the emergence of novel variants that affect epidemiological characteristics globally. Overall, our results stress the importance of rapid equitable vaccine distribution for global control of the pandemic. 

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2. Vaccine stockpile sharing for selfish objectives

   https://doi.org/10.1371/journal.pgph.0001312  

   Shivam, Shashwat; Weitz, Joshua S.; Wardi, Yorai (December 2022, PLOS Global Public Health)

   Mutheneni, Srinivasa Rao (Ed.)

   The COVAX program aims to provide global equitable access to life-saving vaccines. Despite calls for increased sharing, vaccine protectionism has limited progress towards vaccine sharing goals. For example, as of April 2022 only ~20% of the population in Africa had received at least one COVID-19 vaccine dose. Here we use a two-nation coupled epidemic model to evaluate optimal vaccine-sharing policies given a selfish objective: in which countries with vaccine stockpiles aim to minimize fatalities in their own population. Computational analysis of a suite of simulated epidemics reveal that it is often optimal for a donor country to share a significant fraction of its vaccine stockpile with a recipient country that has no vaccine stockpile. Sharing a vaccine stockpile reduces the intensity of outbreaks in the recipient, in turn reducing travel-associated incidence in the donor. This effect is intensified as vaccination rates in a donor country decrease and epidemic coupling between countries increases. Critically, vaccine sharing by a donor significantly reduces transmission and fatalities in the recipient. Moreover, the same computational framework reveals the potential use of hybrid sharing policies that have a negligible effect on fatalities in the donor compared to the optimal policy while significantly reducing fatalities in the recipient. Altogether, these findings provide a self-interested rationale for countries to consider sharing part of their vaccine stockpiles. 

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3. The role of time-varying viral shedding in modelling environmental surveillance for public health: revisiting the 2013 poliovirus outbreak in Israel

   https://doi.org/10.1098/rsif.2022.0006  

   Brouwer, Andrew F.; Eisenberg, Marisa C.; Shulman, Lester M.; Famulare, Michael; Koopman, James S.; Kroiss, Steve J.; Hindiyeh, Musa; Manor, Yossi; Grotto, Itamar; Eisenberg, Joseph N. (May 2022, Journal of The Royal Society Interface)

   Environmental pathogen surveillance is a sensitive tool that can detect early-stage outbreaks, and it is being used to track poliovirus and other pathogens. However, interpretation of longitudinal environmental surveillance signals is difficult because the relationship between infection incidence and viral load in wastewater depends on time-varying shedding intensity. We developed a mathematical model of time-varying poliovirus shedding intensity consistent with expert opinion across a range of immunization states. Incorporating this shedding model into an infectious disease transmission model, we analysed quantitative, polymerase chain reaction data from seven sites during the 2013 Israeli poliovirus outbreak. Compared to a constant shedding model, our time-varying shedding model estimated a slower peak (four weeks later), with more of the population reached by a vaccination campaign before infection and a lower cumulative incidence. We also estimated the population shed virus for an average of 29 days (95% CI 28–31), longer than expert opinion had suggested for a population that was purported to have received three or more inactivated polio vaccine (IPV) doses. One explanation is that IPV may not substantially affect shedding duration. Using realistic models of time-varying shedding coupled with longitudinal environmental surveillance may improve our understanding of outbreak dynamics of poliovirus, SARS-CoV-2, or other pathogens. 

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4. The Impact of Vaccination on Coronavirus Disease 2019 (COVID-19) Outbreaks in the United States

   https://doi.org/10.1093/cid/ciab079  

   Moghadas, Seyed M; Vilches, Thomas N; Zhang, Kevin; Wells, Chad R; Shoukat, Affan; Singer, Burton H; Meyers, Lauren Ancel; Neuzil, Kathleen M; Langley, Joanne M; Fitzpatrick, Meagan C; et al (January 2021, Clinical Infectious Diseases)

   null (Ed.)

   Abstract Background Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. Methods We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. Results Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%–5.0%) from 9.0% (95% CrI: 8.4%–9.4%) without vaccination, over 300 days. The highest relative reduction (54%–62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%–66.7%), 65.6% (95% CrI: 62.2%–68.6%), and 69.3% (95% CrI: 65.5%–73.1%), respectively, across the same period. Conclusions Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact. 

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5. Phage-like particle vaccines are highly immunogenic and protect against pathogenic coronavirus infection and disease

   https://doi.org/10.1038/s41541-022-00481-1  

   Davenport, Bennett J.; Catala, Alexis; Weston, Stuart M.; Johnson, Robert M.; Ardanuy, Jeremy; Hammond, Holly L.; Dillen, Carly; Frieman, Matthew B.; Catalano, Carlos E.; Morrison, Thomas E. (May 2022, npj Vaccines)

   Abstract The response by vaccine developers to the COVID-19 pandemic has been extraordinary with effective vaccines authorized for emergency use in the United States within 1 year of the appearance of the first COVID-19 cases. However, the emergence of SARS-CoV-2 variants and obstacles with the global rollout of new vaccines highlight the need for platforms that are amenable to rapid tuning and stable formulation to facilitate the logistics of vaccine delivery worldwide. We developed a “designer nanoparticle” platform using phage-like particles (PLPs) derived from bacteriophage lambda for a multivalent display of antigens in rigorously defined ratios. Here, we engineered PLPs that display the receptor-binding domain (RBD) protein from SARS-CoV-2 and MERS-CoV, alone (RBD_SARS-PLPs and RBD_MERS-PLPs) and in combination (hCoV-RBD PLPs). Functionalized particles possess physiochemical properties compatible with pharmaceutical standards and retain antigenicity. Following primary immunization, BALB/c mice immunized with RBD_SARS- or RBD_MERS-PLPs display serum RBD-specific IgG endpoint and live virus neutralization titers that, in the case of SARS-CoV-2, were comparable to those detected in convalescent plasma from infected patients. Further, these antibody levels remain elevated up to 6 months post-prime. In dose-response studies, immunization with as little as one microgram of RBD_SARS-PLPs elicited robust neutralizing antibody responses. Finally, animals immunized with RBD_SARS-PLPs, RBD_MERS-PLPs, and hCoV-RBD PLPs were protected against SARS-CoV-2 and/or MERS-CoV lung infection and disease. Collectively, these data suggest that the designer PLP system provides a platform for facile and rapid generation of single and multi-target vaccines. 

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