{"doi":"10.1093/infdis/jiaa234","title":"Balancing Expediency and Scientific Rigor in Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development","abstract":"Over the last 5 months, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated a global health and economic crisis, dramatically altering the daily lives of billions of people. Rapid community transmission of SARS-CoV-2 has been enabled, in part, by its biology and its novelty. Humans have no preexisting immunity to this brand-new human pathogen, and we are all susceptible to infection (though not uniformly likely to develop symptomatic coronavirus disease 2019 [COVID-19]). In the short term, social distancing measures are decreasing community transmission but are exacting enormous costs from individuals and businesses, leading prominent voices to call for lifting restrictive measures. However, as relatively few people are immune to SARS-CoV-2, COVID-19 cases will almost certainly surge if normal activities resume. The only long-term way to control SARS-CoV-2 is for most people to become immune to the virus, so that herd immunity slows down spread. One way to achieve the needed level of protection is for the virus to sweep through the population, at the cost of extensive casualties. Far better would be developing and deploying a safe and effective vaccine to generate widespread immunity, with dual goals of protecting individuals and controlling the pandemic. The COVID-19 pandemic has triggered an explosion of potential vaccine candidates and calls for their rapid and widespread deployment, prompting discussions about the risks of advancing unvetted vaccines into the general population. Fortunately, the process of vaccine licensure is designed to ensure vaccine safety and efficacy, particularly since vaccines are given to healthy people who might never be exposed to SARS-CoV-2 or develop severe disease. The most effective way to identify and deploy efficacious SARS-CoV-2 vaccines with acceptable safety profiles is through carefully designed, scientifically rigorous clinical trials conducted at an accelerated pace. Recent technological advances in vaccine design and global commitments to addressing epidemic diseases have provided a rich infrastructure to support the necessary response to COVID-19. The Moderna messenger RNA vaccine, currently being studied in the United States, was administered to the first human subject just 63 days after the SARS-CoV-2 genetic sequence was released from China. This achievement was facilitated by the acceptable human safety profiles of similar vaccine constructs targeting other diseases, including Zika and avian influenza. Seven other vaccine clinical trials have started in the United States, United Kingdom, Germany, and China, and the list of preclinical vaccine candidates now is 100 [1, 2]. It is not yet clear whether SARS-CoV-2 infection results in durable protective immunity, by what mechanism it might do so, and whether vaccine-elicited immune responses will protect without causing harm. Early studies are promising. Up to 95% of mild COVID-19 cases induce some level of neutralizing antibodies against SARS-CoV-2 [3], and nonhuman primates infected with SARS-CoV-2 are protected from reinfection with the virus [4]. Survivors of infections with related coronaviruses, SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV), developed neutralizing antibodies that persisted for 1–3 years after infection. Phase 1 studies of DNA vaccines for SARS-CoV-1 and MERS-CoV were well tolerated and immunogenic in humans [5, 6]. These reports suggest that SARS-CoV-2 vaccines could safely induce protective immune responses, and it seems likely that 1 or more of the 108 candidate vaccines in development will be ultimately licensed. Yet, there is reason for caution as the experience in animal models is inconclusive. Some SARS-CoV-1 and MERS-CoV vaccine candidates appear to exacerbate illness in animals after subsequent viral challenge [7]. Such vaccine-enhanced disease harks back to respiratory syncytial virus (RSV) and dengue vaccines that caused harm. The mechanisms und","journal":"The Journal of Infectious Diseases","year":2020,"id":71520,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":378162,"name":"Sonali Kochhar","orcid":"0000-0002-1150-5691","position":1,"is_corresponding":false},{"id":368926,"name":"Ellen Wright Clayton","orcid":"0000-0002-0308-4110","position":2,"is_corresponding":false},{"id":379625,"name":"Kathryn E Edwards","orcid":null,"position":3,"is_corresponding":false},{"id":378161,"name":"Kevin W. Graepel","orcid":"0000-0003-2964-5374","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-18T21:44:25.469842Z","pmid":"32365191","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}