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Vaccine

Published: 2024
SYNOPSIS

Global use of inactivated SARS-CoV-2 vaccines with Alum adjuvants have been used in COVID-19 pandemic response, but risk of breakthrough with novel variants and zoonotic reservoirs may lead to adverse outcomes, including VAERD.

TITLE

Adjuvant-dependent effects on the safety and efficacy of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus

M. Heise, J. Dillard, S. Taft-Benz, A. Knight, E. Anderson, K. Pressey, B. Parotti, S. Martinez, J. Diaz, S. Sarkar, E. Madden, G. De la Cruz, L. Adams, K. Dinnon, III, S. Leist, D. Martinez, A. Schaefer, J. Powers, B. Yount, I. Castillo, N. Morales, J. Burdick, M. Katrina Evangelista, L. Ralph, N. Pankow, C. Linnertz, P. Lakshmanane, S. Montgomery, M. Ferris, R. Baric, V. Baxter

 

Inactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 vaccines globally and have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous virus infection in healthy recipients, the emergence of novel SARS-CoV-2 variants and the presence of large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes including vaccine-associated enhanced respiratory disease (VAERD). To evaluate this possibility, we tested the performance of an inactivated SARS-CoV-2 vaccine (iCoV2) in combination with Alum against either homologous or heterologous coronavirus challenge in a mouse model of coronavirus-induced pulmonary disease. Consistent with human results, iCoV2 + Alum protected against homologous challenge. However, challenge with a heterologous SARS-related coronavirus, Rs-SHC014-CoV (SHC014), up to at least 10 months post-vaccination, resulted in VAERD in iCoV2 + Alum-vaccinated animals, characterized by pulmonary eosinophilic infiltrates, enhanced pulmonary pathology, delayed viral clearance, and decreased pulmonary function. In contrast, vaccination with iCoV2 in combination with an alternative adjuvant (RIBI) did not induce VAERD and promoted enhanced SHC014 clearance. Further characterization of iCoV2 + Alum-induced immunity suggested that CD4+ T cells were a major driver of VAERD, and these responses were partially reversed by re-boosting with recombinant Spike protein + RIBI adjuvant. These results highlight potential risks associated with vaccine breakthrough in recipients of Alum-adjuvanted inactivated vaccines and provide important insights into factors affecting both the safety and efficacy of coronavirus vaccines in the face of heterologous virus infections.

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Published: 2023
SYNOPSIS

Vaccines can have beneficial off-target (heterologous) effects that alter immune responses to, and protect against, unrelated infections. The heterologous effects of COVID-19 vaccines have not been investigated in children.

TITLE

BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists

A. Noé, T. D. Dang, C. Axelrad, E. Burrell, S. Germano, S. Elia, D. Burgner, K. P. Perrett, N. Curtis, N. L. Messina

In addition to antigen-specific adaptive immunity to the target pathogen and cross-protective immunity to related microbes (e.g., protection against Mycobacterium tuberculosis and Mycobacterium leprae induced by Mycobacterium bovis-derived bacille Calmette–Guérin (BCG)) (1), vaccines have off-target (heterologous) effects that protect against unrelated pathogens (24).

In high-mortality settings, live-attenuated vaccines are associated with reductions in all-cause infant mortality greater than can be attributed to vaccine-specific protection alone (57). The reduction in all-cause mortality in high-mortality settings is proposed to be due, at least in part, to protection against infections unrelated to the vaccine target (24). Trained immunity, the process by which innate immune cells such as monocytes develop immunological memory through metabolic and epigenetic changes, is one proposed mechanism by which vaccines exert heterologous effects (8, 9). Understanding heterologous effects and trained immunity, and harnessing positive heterologous effects has the potential to extend vaccine-induced protection to a diverse array of pathogens.

The COVID-19 pandemic has prompted a resurgence of interest in the heterologous effects of BCG and other vaccines and compounds (1014). Heterologous immunological effects following vaccination have been explored in several studies by assessing in vitro cytokine responses to heterologous antigens (9, 1519). Two small studies have reported on heterologous effects of COVID-19 vaccines. One study in adults reported that following adenoviral COVID-19 (ChAdOx1) vaccination, monocyte proinflammatory cytokine and chemokine production and glycolysis is enhanced in resting states as well as in response to unrelated stimulants (20). COVID-19 mRNA-based vaccines have been reported to modulate transcriptional profiles in monocytes from adults (21). To date, the heterologous effects of COVID-19 vaccines have not been investigated in children.

In the COVID-19-Specific vaccine and heterologous Immunity in MIS BAIR (COSI BAIR) study (22), we investigated the heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children.

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Published: 2022
SYNOPSIS

Students at North American universities risk disenrollment due to third-dose COVID-19 vaccine mandates. We present a risk-benefit assessment of boosters in this age group and provide five ethical arguments against mandates.

TITLE

COVID-19 Vaccine Boosters for Young Adults: A Risk-Benefit Assessment and Five Ethical Arguments Against Mandates at Universities

K. Bardosh,  A. Krug,  E. Jamrozik, T. Lemmens, S. Keshavjee, V. Prasad, M.A. Makary, S. Baral, H. Stefan, B. Tracy, “COVID-19 Vaccine Boosters for Young Adults: A Risk-Benefit Assessment and Five Ethical Arguments against Mandates at Universities” (August 31, 2022). Available at SSRN: https://ssrn.com/abstract=4206070 or http://dx.doi.org/10.2139/ssrn.4206070

Students at North American universities risk disenrollment due to third-dose COVID-19 vaccine mandates. We present a risk-benefit assessment of boosters in this age group and provide five ethical arguments against mandates. We estimate that 22,000 – 30,000 previously uninfected adults aged 18-29 must be boosted with an mRNA vaccine to prevent one COVID-19 hospitalization. Using CDC and sponsor-reported adverse event data, we find that booster mandates may cause a net expected harm: per COVID-19 hospitalization prevented in previously uninfected young adults, we anticipate 18 to 98 serious adverse events, including 1.7 to 3.0 booster-associated myocarditis cases in males, and 1,373 to 3,234 cases of grade ≥3 reactogenicity which interferes with daily activities. Given the high prevalence of post-infection immunity, this risk-benefit profile is even less favorable. University booster mandates are unethical because: 1) no formal risk-benefit assessment exists for this age group; 2) vaccine mandates may result in a net expected harm to individual young people; 3) mandates are not proportionate: expected harms are not outweighed by public health benefits given the modest and transient effectiveness of vaccines against transmission; 4) US mandates violate the reciprocity principle because rare serious vaccine-related harms will not be reliably compensated due to gaps in current vaccine injury schemes; and 5) mandates create wider social harms. We consider counter-arguments such as a desire for socialization and safety and show that such arguments lack scientific and/or ethical support. Finally, we discuss the relevance of our analysis for current 2-dose Covid-19 vaccine mandates in North America.

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