Study: Breakthrough COVID-19 Infections Spur Strong Antibody Responses

Investigators learned that the degree of response depended on whether an individual has had 1, 2, 3, or 4, exposures through infection, vaccination, or both.

The degree of antibody response in COVID-19 depends on whether an individual has had 1, 2, 3, or 4 exposures to the spike protein through infection, vaccination, or both, according to new study results published in Cell.

The investigators, led by David Veesler and Alexandra Walls of the Department of Biochemistry at the University of Washington in Seattle, also checked antibody responses in groups of individuals who had been vaccinated after having COVID-19, those who were previously vaccinated and experienced a breakthrough infection, those who were vaccinated only, and those who were boosted and therefore vaccinated 3 times, according to a statement.

Among their study subjects, individuals who had completed a 3-vaccination protocol, those who had been vaccinated after recovering from COVID-19, and those with a breakthrough infection after vaccination launched almost comparable neutralizing antibody responses, in terms of breadth and magnitude. Their serum binding and antibody neutralizing responses to the spike protein in the COVID-19 variants were much more lasting and potent than those generated by individuals who had received just 2 vaccine doses or who had a previous infection not followed by vaccination.

This observation suggested that the increased number of exposures to SARS-CoV-2 antigens, either through infection and vaccination or triple vaccination, enhanced the quality of antibody responses.

The investigators also looked at how broad the elicited antibodies could be. They investigated neutralization of the divergent omicron SARS-CoV-2 variant of concern, which is responsible for most recent cases in the United States. Their findings showed that boosted individuals, or those who have a mixture of double vaccination and infection, have neutralizing antibodies at similar levels to subjects vaccinated twice against the original ancestral strain. This suggests a large amount of immune evasion but that vaccine boosters can help close the neutralizing antibody gap caused by omicron.

The characteristics of the Delta and omicron variants have led to many breakthrough infections in vaccinated individuals. The variants have enhanced immune easion and transmissibility, even in non-immunologically naïve individuals when compared with the ancestral pandemic coronavirus.

For the most part, healthy individuals who are vaccinated against SARS-CoV-2 do not have severe symptoms if they contract the virus.

Looking outside the SARS-CoV-2 family shows a similar pattern, where multiple and repeated exposures improve the otherwise weak neutralizing antibody response to SARS-CoV. Finally, the investigators did not identify improvements in antibody binding to common cold-causing coronavirus spike proteins, such as HKU1 or OC43. This suggests that repeated SARS-CoV-2 exposure does not improve spike reactivity to more divergent coronaviruses. These findings support the development of broader coronavirus or sarbecovirus vaccines be prepared in the event of a future spillover event.

The study groups consisted of 15 individuals, from the Hospitalized or Ambulatory Adults with Respiratory Viral Infections (HAARVI) project at the University of Washington in Seattle. HAARVI looks at recovered COVID-19 patients to study immune responses over time, to compare immune responses from natural infections and vaccines and understand the long-term consequences of the infection.

Investigators aimed to examine the breadth, durability, and strength of neutralizing antibody responses generated by breakthrough infections in individuals vaccinated against SARS-CoV-2. They hope that the findings will help guide pandemic mitigation strategies and vaccination policies.


Breakthrough COVID-19 infections spur strong antibody responses. EurekAlert. News release. January 21, 2022. Accessed January 25, 2022.