Pathogen transmission from vaccinated hosts can cause dose-dependent reduction in virulence

Bailey, Richard I.; Cheng, H. H.; Chase-Topping, Margo; Mays, Jody K.; Anacleto, Osvaldo; Dunn, John R.; Doeschl‐Wilson, Andrea

doi:10.1101/830570

Cited by 8 publications

(10 citation statements)

References 64 publications

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“…In particular, the vaccinal strain used in this study was shown to reduce nasal viral load and thus likely also host infectivity, as well as the duration of the infectious period with likely subsequent effects on R0. However, the results of our study also suggest that incomplete effective vaccine coverage may have less impact on the transmission dynamics than predicted by theory, as viral shedding and thus potentially infectivity of non-vaccinated individuals may be reduced if their infectious contacts are vaccinated [40]. Such indirect effects of vaccination are currently not incorporated in typical epidemiological prediction models.…”

Section: Discussionmentioning

confidence: 58%

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New insights about vaccine effectiveness: Impact of attenuated PRRS-strain vaccination on heterologous strain transmission

Chase-Topping

Xie

Pooley

et al. 2020

Vaccine

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Vaccination is the main tool for controlling infectious diseases in livestock. Yet current vaccines only provide partial protection raising concerns about vaccine effectiveness in the field.Two successive transmission trials were performed involving 52 pigs to evaluate the effectiveness of a Porcine Reproductive and Respiratory Syndrome (PRRS) vaccinal strain candidate against horizontal transmission of a virulent heterologous strain. PRRS virus, above the specified limit of detection, was observed in serum and nasal secretions for all but one pig (the exception only tested positive for serum), indicating that vaccination did not protect pigs from becoming infected and shedding the heterologous strain. However, vaccination delayed the onset of viraemia, reduced the duration of shedding and significantly decreased viral load throughout infection. Serum antibody profiles indicated that 4 out of 13 (31%) vaccinates in one trial had no serological response (NSR).A Bayesian epidemiological model was fitted to the data to assess the impact of vaccination, and presence of NSRs, on PRRS virus transmission dynamics.Despite little evidence for reduction in the transmission rate, vaccinated animals were on average slower to become infectious, experienced a shorter infectious period and recovered faster. The overall PRRSV transmission potential, represented by the reproductive ratio R0 was lower for the vaccinated animals, although there was substantial overlap in the credibility intervals for both groups. Model selection suggests that transmission parameters of vaccinated pigs with NSR were more similar to those of unvaccinated animals. The presence of NSRs in a population, however, seemed to only marginally affect the transmission dynamics.The results suggest that even when vaccination can't prevent infection, it can still have beneficial impacts on the transmission dynamics and contribute to reducing a herd's R0. However, biosecurity and other measures need to be considered to decrease contact rates and lower R0 below 1.

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Section: Discussionmentioning

confidence: 58%

“…Only few studies have evaluated virus transmission using contact models (PRRSV [5,38,39]; Marek's Disease [40]; FMD [41]; Avian flu [42]; Swine flu [43]).…”

Section: Discussionmentioning

confidence: 99%

New insights about vaccine effectiveness: Impact of attenuated PRRS-strain vaccination on heterologous strain transmission

Chase-Topping

Xie

Pooley

et al. 2020

Vaccine

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“…Reduced VE INF anticipates that symptomatic breakthrough infections in vaccine recipients may be associated with fewer secondary transmissions than in placebo recipients, and that people who develop asymptomatic rather than symptomatic infection due to vaccination (VE SYMP ) may also be less likely to transmit. This latter observation would be expected if a vaccine mediates reduction in both symptoms and secondary transmission potential by lowering the quantity of viral shedding ( 11 ). While high VE DIS guarantees a high likelihood of individual benefit, protection of unvaccinated members of the population will also depend on VE SUSC and VE INF , as well as the velocity of a vaccination roll out program ( 8, 12 ).…”

Section: Introductionmentioning

confidence: 91%

Vaccines that prevent SARS-CoV-2 transmission may prevent or dampen a spring wave of COVID-19 cases and deaths in 2021

Swan

Goyal

Bracis

et al. 2020

Preprint

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Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VEDIS), the ability of a vaccine to block symptomatic COVID-19. They will only partially discriminate whether VEDIS is mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VESUSC), or by preventing symptoms despite breakthrough infection (vaccine efficacy against symptoms or VESYMP). Vaccine efficacy against infectiousness (VEINF), defined as the decrease in secondary transmissions from infected vaccine recipients versus from infected placebo recipients, is also not being measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna and Pfizer vaccines, which have observed VEDIS>90%, mediate VEDIS predominately by complete protection against infection, then prevention of a fourth epidemic wave in the spring of 2021, and associated reduction of subsequent cases and deaths by 60%, is likely to occur assuming rapid enough vaccine roll out. If high VEDIS is explained primarily by reduction in symptoms, then VEINF>50% will be necessary to prevent or limit the extent of this fourth epidemic wave. The potential added benefits of high VEINF would be evident regardless of vaccine allocation strategy and would be enhanced if vaccine roll out rate is low or if available vaccines demonstrate waning immunity. Finally, we demonstrate that a 1.0 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve VEINF=60% and that human challenge studies with 104 infected participants, or clinical trials in a university student population could estimate VESUSC, VESYMP and VEINF using viral load metrics.

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“…Marek's disease (MD) is a serious cancer caused by Marek's disease virus (MDV), which is an oncogenic alpha herpesvirus. In addition to causing a large number of deaths, it can also cause a low feed conversion rate, weight loss, egg production reduction, and immunosuppression, leading to secondary infection of other pathogens in chickens (1)(2)(3)(4). MD was first described a hundred years ago, and after decades of research, scholars have made great efforts in understanding the genomics(5-7), serology (8), viral lifecycle (9,10), pathogenesis of cancer (11,12), vaccinology and virus mutation mechanism of MDV (13,14).…”

Section: Introductionmentioning

confidence: 99%

“…As a consequence, vaccinated chickens still become infected and shed the virus into the environment (33). In addition, the vaccine itself can also replicate and shed in chickens (2,34). Thus, the live-attenuated vaccine can reduce mortality and prolong the survival time of infected chickens, but it does not significantly reduce the virus excretion rate (35).…”

Section: Introductionmentioning

confidence: 99%

Structural and immunological identification and antiviral infection experiment of the dominant cytotoxic T lymphocyte epitopes of the oncogenic Marek’s disease virus

Sun

Wang²,

Wang³

et al. 2021

Preprint

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Marek’s disease (MD) is a serious cancer caused by MDV in chickens, and it is also the first tumor disease that could be controlled by an attenuated vaccine in the world. However, the attenuated vaccine is able to inhibit only the formation of tumors but cannot prevent the infection of oncogenic viruses; instead, it leads to mutations and the emergence of a number of virulent strains. In this paper, the crystal structures of chicken MHC class I (pBF2*1501) molecules bound with 8-mer and 9-mer MDV peptides were solved. The results showed that the conformations of the 8-mer and 9-mer peptides in the antigen-binding groove (ABG) of pBF2*1501 are different; the ABG-8-mer is flat, and the ABG-9-mer has the “featured” M-type epitope morphology. Based on these results, multiple MDV epitopes were confirmed using the tetramer technique, and the immunoprotective effect of dominant epitope was confirmed using the protein adjuvant HSP108-N333 in BF2*1501-expressing chickens. The results showed that the two epitopes have obvious protective effects after a standard immunization program. After challenge, the mortality rate was only 20%, and the protective index (PI) reached 33% in the epitope group. The results verified that a single epitope could induce extremely strong specific antitumor T lymphocyte immunity. The results show that three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant cytotoxic T lymphocyte (CTL) epitopes, efficient protein adjuvant and MHC matching. Meanwhile, the results also provided obvious advantages for the development of multiple epitope vaccines for tumor diseases.ImportanceMarek’s disease (MD) is the first tumor disease that can be controlled by an attenuated vaccine. However, the attenuated vaccine cannot prevent the infection of the oncogenic virus and instead leads to the emergence of a number of mutated virulent strains. First, the mechanism of the chicken BF2*1501 preferentially presents 9-mer peptide was clarified. Based on this result, multiple MDV epitopes were confirmed, and the dominant epitopes were identified. Subsequently, two epitope groups showed obvious protective effects after a standard immunization program, and the protective index (PI) of one of the epitope groups reached over 30%. The results showed that a single epitope could induce strong and efficient antitumor CTL immunity. Overall, three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant epitopes, efficient protein adjuvant and MHC matching. Our results provide an obvious strategy for the development of multiple epitope vaccines in tumor diseases.

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Pathogen transmission from vaccinated hosts can cause dose-dependent reduction in virulence

Abstract: 2 1 Many livestock and human vaccines are leaky as they block symptoms but do not 2 2 0 *

Cited by 8 publications

References 64 publications

New insights about vaccine effectiveness: Impact of attenuated PRRS-strain vaccination on heterologous strain transmission

New insights about vaccine effectiveness: Impact of attenuated PRRS-strain vaccination on heterologous strain transmission

Vaccines that prevent SARS-CoV-2 transmission may prevent or dampen a spring wave of COVID-19 cases and deaths in 2021

Structural and immunological identification and antiviral infection experiment of the dominant cytotoxic T lymphocyte epitopes of the oncogenic Marek’s disease virus

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