skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes
In the face of vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to SARS-CoV-2. Two critical issues arise: how will the timing of delivery of the second dose affect both infection dynamics and prospects for the evolution of viral immune escape via a build-up of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose, compared to natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short-term, focusing on one dose generally decreases infections, but longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose, and to ramp up vaccination efforts throughout the world.  more » « less
Award ID(s):
1917819 2027908
PAR ID:
10218317
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Science
ISSN:
0036-8075
Page Range / eLocation ID:
eabg8663
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Wallqvist, Anders (Ed.)
    The SARS-CoV-2 pandemic has generated a considerable number of infections and associated morbidity and mortality across the world. Recovery from these infections, combined with the onset of large-scale vaccination, have led to rapidly-changing population-level immunological landscapes. In turn, these complexities have highlighted a number of important unknowns related to the breadth and strength of immunity following recovery or vaccination. Using simple mathematical models, we investigate the medium-term impacts of waning immunity against severe disease on immuno-epidemiological dynamics. We find that uncertainties in the duration of severity-blocking immunity (imparted by either infection or vaccination) can lead to a large range of medium-term population-level outcomes (i.e. infection characteristics and immune landscapes). Furthermore, we show that epidemiological dynamics are sensitive to the strength and duration of underlying host immune responses; this implies that determining infection levels from hospitalizations requires accurate estimates of these immune parameters. More durable vaccines both reduce these uncertainties and alleviate the burden of SARS-CoV-2 in pessimistic outcomes. However, heterogeneity in vaccine uptake drastically changes immune landscapes toward larger fractions of individuals with waned severity-blocking immunity. In particular, if hesitancy is substantial, more robust vaccines have almost no effects on population-level immuno-epidemiology, even if vaccination rates are compensatorily high among vaccine-adopters. This pessimistic scenario for vaccination heterogeneity arises because those few individuals that are vaccine-adopters are so readily re-vaccinated that the duration of vaccinal immunity has no appreciable consequences on their immune status. Furthermore, we find that this effect is heightened if vaccine-hesitants have increased transmissibility (e.g. due to riskier behavior). Overall, our results illustrate the necessity to characterize both transmission-blocking and severity-blocking immune time scales. Our findings also underline the importance of developing robust next-generation vaccines with equitable mass vaccine deployment. 
    more » « less
  2. We investigate the impact of differential vaccine effectiveness, waning immunity, and natural cross-immunity on the capacity for vaccine-induced strain replacement in two-strain models of infectious disease spread. We focus specifically on the case where the first strain is more transmissible but the second strain is more immune-resistant. We consider two cases on vaccine-induced immunity: (1) a monovalent model where the second strain has immune escape with respect to vaccination; and (2) a bivalent model where the vaccine remains equally effective against both strains. Our analysis reaffirms the capacity for vaccine-induced strain replacement under a variety of circumstances; surprisingly, however, we find that which strain is preferred depends sensitively on the degree of differential vaccine effectiveness. In general, the monovalent model favors the more immune-resistant strain at high vaccination levels while the bivalent model favors the more transmissible strain at high vaccination levels. To further investigate this phenomenon, we parametrize the bifurcation space between the monovalent and bivalent model. 
    more » « less
  3. As the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer-term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or ‘evolution-proof’) immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real-world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable and broadly protective vaccine. 
    more » « less
  4. Vaccines are a pivotal achievement in public health, offering inexpensive, distributable and highly effective protection against infectious diseases. Despite significant advancements in vaccine development, there are still many diseases for which vaccines are unavailable or offer limited protection. The global impact of the deficiency in vaccine‐induced immunity against these diseases is profound, leading to increased rates of illness, more frequent hospitalizations, and higher mortality rates. Recent studies have demonstrated conjugation mechanisms and delivery methods to co‐present adjuvants and protein epitopes to antigen‐presenting cells, significantly enhancing adaptive immunity. We introduce a novel approach to incorporate an adjuvant into the vaccine by covalently attaching it to whole enveloped virions. Using clickable azide‐enabled viral particles, generated through metabolic incorporation of N‐azidoacetyl glucosamine (GlcNAz), we conjugated the virions with a cyclo‐octyne‐modified CpG‐ODN. Conjugation yielded a potent adjuvant‐virus complex, eliciting higher TLR9‐mediated cell activation of cultured bone marrow‐derived macrophages relative to co‐administered adjuvants and virions. Administration of covalent adjuvant‐virion conjugates increase immune cell stimulation and may provide a generalizable and effective strategy for eliciting a heightened immune response for vaccine development. 
    more » « less
  5. Kolawole, Olatunji Matthew (Ed.)
    As the COVID-19 pandemic progresses, widespread community transmission of SARS-CoV-2 has ushered in a volatile era of viral immune evasion rather than the much-heralded stability of “endemicity” or “herd immunity.” At this point, an array of viral strains has rendered essentially all monoclonal antibody therapeutics obsolete and strongly undermined the impact of vaccinal immunity on SARS-CoV-2 transmission. In this work, we demonstrate that antibody escape resulting in evasion of pre-existing immunity is highly evolutionarily favored and likely to cause waves of short-term transmission. In the long-term, invading strains that induce weak cross-immunity against pre-existing strains may co-circulate with those pre-existing strains. This would result in the formation of serotypes that increase disease burden, complicate SARS-CoV-2 control, and raise the potential for increases in viral virulence. Less durable immunity does not drive positive selection as a trait, but such strains may transmit at high levels if they establish. Overall, our results draw attention to the importance of inter-strain cross-immunity as a driver of transmission trends and the importance of early immune evasion data to predict the trajectory of the pandemic. 
    more » « less