Vaccine-associated Enhanced Respiratory Disease

Vaccine-associated enhanced respiratory disease (VAERD), or simply enhanced respiratory disease (ERD), is an adverse event where an exacerbated course of respiratory disease occurs with higher incidence in the vaccinated population than in the control group. It is a barrier against vaccine development that can lead to its failure.^[1]

Immunologically, VAERD is characterized with an exaggerated Th2 response and eosinophilic pulmonary infiltrations.^[2] It may result from antibody-mediated complement activation followed by weak neutralization.^[3]

Historical instances of the phenomenon were seen in vaccine candidates for respiratory syncytial virus (RSV), SARS-CoV, Middle East Respiratory Syndrome (MERS), and some influenza strains.^[1]^[4]^[5] Thus, COVID-19 vaccine clinical research involved monitoring for VAERD because the vaccine target, SARS-CoV-2, belongs to the same viral subfamily as SARS-CoV and MERS. The effect was not shown in phase III clinical trials for Tozinameran or for the Moderna vaccine.^[2]^[6]

References

^ ^a ^b Acosta, Patricio L.; Caballero, Mauricio T.; Polack, Fernando P.; Papasian, C. J. (2016). "Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease". Clinical and Vaccine Immunology. 23 (3): 189–195. doi: 10.1128/CVI.00609-15. ISSN 1556-6811. PMC 4783420. PMID 26677198.
^ ^a ^b Baden, Lindsey R.; El Sahly, Hana M.; Essink, Brandon; Kotloff, Karen; Frey, Sharon; Novak, Rick; Diemert, David; Spector, Stephen A.; Rouphael, Nadine; Creech, C. Buddy; McGettigan, John; Khetan, Shishir; Segall, Nathan; Solis, Joel; Brosz, Adam; Fierro, Carlos; Schwartz, Howard; Neuzil, Kathleen; Corey, Larry; Gilbert, Peter; Janes, Holly; Follmann, Dean; Marovich, Mary; Mascola, John; Polakowski, Laura; Ledgerwood, Julie; Graham, Barney S.; Bennett, Hamilton; Pajon, Rolando; Knightly, Conor; Leav, Brett; Deng, Weiping; Zhou, Honghong; Han, Shu; Ivarsson, Melanie; Miller, Jacqueline; Zaks, Tal (2021). "Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine". New England Journal of Medicine. 384 (5): 403–416. doi: 10.1056/NEJMoa2035389. ISSN 0028-4793. PMC 7787219. PMID 33378609.
^ Richard W. Compans; Michael B. A. Oldstone (8 October 2014). Influenza Pathogenesis and Control - Volume I. Springer. pp. 315–320. ISBN 978-3-319-11155-1.
^ Agrawal, Anurodh Shankar; Tao, Xinrong; Algaissi, Abdullah; Garron, Tania; Narayanan, Krishna; Peng, Bi-Hung; Couch, Robert B.; Tseng, Chien-Te K. (2016). "Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus". Human Vaccines & Immunotherapeutics. 12 (9): 2351–2356. doi: 10.1080/21645515.2016.1177688. ISSN 2164-5515. PMC 5027702. PMID 27269431.
^ Bottazzi, Maria Elena; Strych, Ulrich; Hotez, Peter J.; Corry, David B. (2020). "Coronavirus vaccine-associated lung immunopathology-what is the significance?". Microbes and Infection. 22 (9): 403–404. doi: 10.1016/j.micinf.2020.06.007. ISSN 1286-4579. PMC 7318931. PMID 32599077.
^ FDA Review of Efficacy and Safety of Pfizer-BioNTech COVID-19 Vaccine Emergency Use Authorization Request (PDF). U.S. Food and Drug Administration (FDA) (Report). 10 December 2020. Retrieved 11 December 2020.

[AcostaCaballero2016-1] Acosta, Patricio L.; Caballero, Mauricio T.; Polack, Fernando P.; Papasian, C. J. (2016). "Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease". Clinical and Vaccine Immunology. 23 (3): 189–195. doi: 10.1128/CVI.00609-15. ISSN 1556-6811. PMC 4783420. PMID 26677198.

[BadenEl_Sahly2021-2] Baden, Lindsey R.; El Sahly, Hana M.; Essink, Brandon; Kotloff, Karen; Frey, Sharon; Novak, Rick; Diemert, David; Spector, Stephen A.; Rouphael, Nadine; Creech, C. Buddy; McGettigan, John; Khetan, Shishir; Segall, Nathan; Solis, Joel; Brosz, Adam; Fierro, Carlos; Schwartz, Howard; Neuzil, Kathleen; Corey, Larry; Gilbert, Peter; Janes, Holly; Follmann, Dean; Marovich, Mary; Mascola, John; Polakowski, Laura; Ledgerwood, Julie; Graham, Barney S.; Bennett, Hamilton; Pajon, Rolando; Knightly, Conor; Leav, Brett; Deng, Weiping; Zhou, Honghong; Han, Shu; Ivarsson, Melanie; Miller, Jacqueline; Zaks, Tal (2021). "Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine". New England Journal of Medicine. 384 (5): 403–416. doi: 10.1056/NEJMoa2035389. ISSN 0028-4793. PMC 7787219. PMID 33378609.

[CompansOldstone2014-3] Richard W. Compans; Michael B. A. Oldstone (8 October 2014). Influenza Pathogenesis and Control - Volume I. Springer. pp. 315–320. ISBN 978-3-319-11155-1.

[AgrawalTao2016-4] Agrawal, Anurodh Shankar; Tao, Xinrong; Algaissi, Abdullah; Garron, Tania; Narayanan, Krishna; Peng, Bi-Hung; Couch, Robert B.; Tseng, Chien-Te K. (2016). "Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus". Human Vaccines & Immunotherapeutics. 12 (9): 2351–2356. doi: 10.1080/21645515.2016.1177688. ISSN 2164-5515. PMC 5027702. PMID 27269431.

[BottazziStrych2020-5] Bottazzi, Maria Elena; Strych, Ulrich; Hotez, Peter J.; Corry, David B. (2020). "Coronavirus vaccine-associated lung immunopathology-what is the significance?". Microbes and Infection. 22 (9): 403–404. doi: 10.1016/j.micinf.2020.06.007. ISSN 1286-4579. PMC 7318931. PMID 32599077.

[6] FDA Review of Efficacy and Safety of Pfizer-BioNTech COVID-19 Vaccine Emergency Use Authorization Request (PDF). U.S. Food and Drug Administration (FDA) (Report). 10 December 2020. Retrieved 11 December 2020.

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