Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers

Shamier, Marc C.; Tostmann, Alma; Bogers, Susanne; Wilde, Janet de; IJpelaar, Jeroen; Kleij, Willemijn A. van der; Jager, Herbert de; Haagmans, Bart L.; Molenkamp, Richard; Munnink, Bas B. Oude; Rossum, Carsten van; Rahamat‐Langendoen, Janette; Geest, Nannet van der; Bleeker‐Rovers, Chantal P.; Wertheim, Heiman; GeurtsvanKessel, Corine H.

doi:10.1101/2021.08.20.21262158

Cited by 58 publications

(52 citation statements)

References 25 publications

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“…For samples with Cn values below 27, we found that the probability of being viral culture positive was lower for samples coming from vaccinated individuals versus newly vaccinated and unvaccinated individuals. These data suggest that for a given viral genome load (as measured by RTqPCR), vaccinated individuals may be less infectious than unvaccinated individuals, consistent with a recent report examining Delta breakthrough infections 8 . However, we must emphasize that this difference is not statistically significant, potentially due to both the relatively small number of samples from vaccinees and the fact that only 6 out of 12 individuals included in the vaccinated group were fully vaccinated at the time of enrollment.…”

Section: Main Textsupporting

confidence: 88%

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

Martinez

Smith

et al. 2021

Preprint

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The global effort to vaccinate people against SARS-CoV-2 in the midst of an ongoing pandemic has raised questions about the nature of vaccine breakthrough infections and the potential for vaccinated individuals to transmit the virus. These questions have become even more urgent as new variants of concern with enhanced transmissibility, such as Delta, continue to emerge. To shed light on how vaccine breakthrough infections compare with infections in immunologically naive individuals, we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. These data indicate that vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

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Section: Main Textsupporting

confidence: 88%

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

Martinez

Smith

et al. 2021

Preprint

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“…17,[27][28][29][30] In addition, vaccinated individuals with a breakthrough infection are less infectious than unvaccinated individuals. 31 The particles emitted by these individuals might be less infectious through induction of antibodies that can coat the virus, which, through steric hindrance or complement fixation, can prevent virions from infecting susceptible hosts. The extent of vaccine-induced transmission blockade can be studied through contact-tracing studies comparing exposed, vaccinated with exposed, unvaccinated individuals.…”

Section: Effect Of Sars-cov-2 Vaccination On Host-to-host Transmissionmentioning

confidence: 99%

Prevention of host-to-host transmission by SARS-CoV-2 vaccines

Mostaghimi

Valdez

Larson

et al. 2022

The Lancet Infectious Diseases

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As the number of individuals vaccinated against SARS-CoV-2 rises worldwide, population-level data regarding the vaccines' ability to reduce infection are being generated. Randomised trials have shown that these vaccines dramatically reduce symptomatic COVID-19; however, less is known about their effects on transmission between individuals. The natural course of infection with SARS-CoV-2 involves infection of the respiratory epithelia and replication within the mucosa to sufficient viral titres for transmission via aerosol particles and droplets. Here we discuss the available data on the existing, approved SARS-CoV-2 vaccines' capacity to reduce transmissibility by reducing primary infection, viral replication, capacity for transmission, and symptomaticity. The potential for mucosal-targeted SARS-CoV-2 vaccine strategies to more effectively limit transmission than intramuscular vaccines is considered with regard to known immunological mechanisms. Finally, we enumerate the population-level effects of approved vaccines on transmission through observational studies following clinical trials and vaccine distribution in real-world settings.

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“…By responding and restricting viral infection within the first hours to days after exposure, cellular immunity can thereby reduce or even prevent symptoms of disease (i.e. preventing hospitalization and death) and potentially reduce the ability to spread virus to others ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern

Goel

Painter

Apostolidis

et al. 2021

Preprint

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SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naive and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.

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Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers

Cited by 58 publications

References 25 publications

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

Prevention of host-to-host transmission by SARS-CoV-2 vaccines

mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern

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