Market design to accelerate COVID-19 vaccine supply Castillo, Juan Camilo; Ahuja, Amrita; Athey, Susan ...
Science (American Association for the Advancement of Science),
03/2021, Volume:
371, Issue:
6534
Journal Article
We derive the optimal funding mechanism to incentivize development and production of vaccines against diseases with epidemic potential. In the model, suppliers’ costs are private information and ...investments are noncontractible, precluding cost-reimbursement contracts, requiring fixed-price contracts conditioned on delivery of a successful product. The high failure risk for individual vaccines calls for incentivizing multiple entrants, accomplished by the optimal mechanism, a (w+1)-price reverse Vickrey auction with reserve, where w is the number of selected entrants. Our analysis determines the optimal number of entrants and required funding level. Based on a distribution of supplier costs estimated from survey data, we simulate the optimal mechanism’s performance in scenarios ranging from a small outbreak, causing harm in the millions of dollars, to the Covid-19 pandemic, causing harm in the trillions. We assess which mechanism features contribute most to its optimality.
People differ in their ability to perform novel perceptual tasks, both during initial exposure and in the rate of improvement with practice. It is also known that regions of the brain recruited by ...particular tasks change their activity during learning. Here we investigate neural signals predictive of individual variability in performance. We used resting-state functional MRI to assess functional connectivity before training on a novel visual discrimination task. Subsequent task performance was related to functional connectivity measures within portions of visual cortex and between visual cortex and prefrontal association areas. Our results indicate that individual differences in performing novel perceptual tasks can be related to individual differences in spontaneous cortical activity.
Several low-grade persistent viral infections induce and sustain very large numbers of virus-specific effector T cells. This was first described as a response to cytomegalovirus (CMV), a herpesvirus ...that establishes a life-long persistent/latent infection, and sustains the largest known effector T cell populations in healthy people. These T cells remain functional and traffic systemically, which has led to the recent exploration of CMV as a persistent vaccine vector. However, the maintenance of this remarkable response is not understood. Current models propose that reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and effector differentiation, followed by migration of progeny to non-lymphoid tissues where they control CMV reactivation. We tested this model using murine CMV (MCMV), a natural mouse pathogen and homologue of human CMV (HCMV). While T cells within draining lymph nodes divided at a higher rate than cells elsewhere, antigen-dependent proliferation of MCMV-specific effector T cells was observed systemically. Strikingly, inhibition of T cell egress from lymph nodes failed to eliminate systemic T cell division, and did not prevent the maintenance of the inflationary populations. In fact, we found that the vast majority of inflationary cells, including most cells undergoing antigen-driven division, had not migrated into the parenchyma of non-lymphoid tissues but were instead exposed to the blood supply. Indeed, the immunodominance and effector phenotype of inflationary cells, both of which are primary hallmarks of memory inflation, were largely confined to blood-localized T cells. Together these results support a new model of MCMV-driven memory inflation in which most immune surveillance occurs in circulation, and in which most inflationary effector T cells are produced in response to viral antigen presented by cells that are accessible to the blood supply.
A widely accessible vaccine is essential to mitigate the health and economic ravages of coronavirus disease 2019 (COVID-19). Without appropriate incentives and coordination, however, firms might not ...respond at sufficient speed or scale, and competition among countries for limited supply could drive up prices and undercut efficient allocation. Programs relying on "push" incentives (direct cost reimbursement) can be complicated by the funder's inability to observe firms' private cost information. To address these challenges, we propose a "pull" program that incentivizes late-stage development (Phase III trials and manufacturing) for COVID-19 vaccines by awarding advance purchase agreements to bidding firms. Using novel cost and demand data, we calculated the optimal size and number of awards. In baseline simulations, the optimal program induced the participation of virtually all ten viable vaccine candidates, spending an average of $110 billion to generate net benefits of $2.8 trillion-nearly double the net benefits generated by the free market.
In religious philosophy, the concept of karma represents the effect of one's past and present actions on one's future. Macrophages are highly plastic cells with myriad roles in health and disease. In ...the setting of cancer, macrophages are among the most plentiful members of the immune microenvironment where they generally support tumor growth and restrain antitumor immunity. However, macrophages are not necessarily born bad. Macrophages or their immediate progenitors, monocytes, are induced to traffic to the tumor microenvironment (TME) and during this process they are polarized toward a tumor-promoting phenotype. Efforts to deplete or repolarize tumor-associated macrophages (TAM) for therapeutic benefit in cancer have to date disappointed. By contrast, genetic engineering of macrophages followed by their transit into the TME may allow these impressionable cells to mend their ways. In this review, we summarize and discuss recent advances in the genetic engineering of macrophages for the treatment of cancer.
An open‐access journal allows free online access to its articles, obtaining revenue from fees charged to submitting authors or from institutional support. Using panel data on science journals, we are ...able to circumvent problems plaguing previous studies of the impact of open access on citations. In contrast to the huge effects found in these previous studies, we find a more modest effect: moving from paid to open access increases cites by 8% on average in our sample. The benefit is concentrated among top‐ranked journals. In fact, open access causes a statistically significant reduction in cites to the bottom‐ranked journals in our sample, leading us to conjecture that open access may intensify competition among articles for readers' attention, generating losers as well as winners. (JEL L17, O33)
PREVENTIVES VERSUS TREATMENTS Kremer, Michael; Snyder, Christopher M.
The Quarterly journal of economics,
08/2015, Volume:
130, Issue:
3
Journal Article
Peer reviewed
Preventives are sold ex ante, before disease status is realized, while treatments are sold ex post. Even if the mean of the ex ante distribution of consumer values is the same as that ex post, the ...shape of the distributions may differ, generating a difference between the surplus each product can extract. If, for example, consumers differ only in ex ante disease risk, then a monopolist would have more difficulty extracting surplus with a preventive than with a treatment because treatment consumers, having contracted the disease, no longer differ in disease risk. We show that the ratio of preventive to treatment producer surplus can be arbitrarily small, in particular when the distribution of consumer values has a Zipf shape and the disease is rare. The firm’s bias toward treatments can be reversed, for example, if the source of private information is disease severity learned ex post. The difference between the producer surplus earned from the products can result in distorted R&D incentives; the deadweight loss from this distortion can be as large as the entire producer-surplus difference. Calibrations for HIV and heart attacks based on risk factors in the U.S. population suggest that the distribution of disease risk is sufficiently Zipf-similar to generate substantial differences between producer surplus from preventives and treatments. Empirically, we find that proxies for the Zipf-similarity of the disease-risk distribution are associated a significantly lower likelihood of vaccine development but not drug development.
Cytomegalovirus (CMV) is a herpesvirus that persists for life and maintains extremely large numbers of T cells with select specificities in circulation. However, it is unknown how viral persistence ...impacts T cell populations in mucosal sites. We found that many murine (M)CMV-specific CD8s in mucosal tissues became resident memory T cells (TRM). These cells adopted an intraepithelial localization in the salivary gland that correlated with, but did not depend on, expression of the integrin CD103. MCMV-specific TRM cells formed early after infection, and spleen-localized cells had reduced capacities to become TRM at late times. Surprisingly, however, small numbers of new TRM cells were formed from the circulating pool throughout infection, favoring populations maintained at high levels in the blood and shifting the immunodominance within the TRM populations over time. These data show that mucosal TRM populations can be dynamically maintained by a persistent infection.
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•MCMV induces resident memory CD8s in multiple mucosal tissues early after infection•TRM maintenance and IEL localization in the salivary gland does not depend on CD103•MCMV-specific CD8s circulating during latency have reduced capacity to form new TRM•Antigen promotes the late recruitment and formation of TRM in the salivary gland
Cytomegalovirus (CMV) is shed from the salivary gland and other mucosal tissues, yet the CD8 response at these sites is poorly understood. Smith et al. show that MCMV-specific tissue-resident CD8 populations are supported by continuous, low-level recruitment of circulating CD8s that become TRM in an antigen-dependent manner.
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