Neutralizing the foe: tracking the immune response to SARS-CoV-2 infection

From the Bloom Lab, Basic Sciences Division

In times of stress and danger such as come about as the result of an epidemic, many tragic and cruel phases of human nature are brought out, as well as many brave and unselfish ones.   -William Crawford Gorgas

All crises bring out the best and worst of human nature. In its devastation, SARS-CoV-2 has birthed a new generation of heroes and villains: anti-maskers or, depending on one’s views, overly restrictive state and local governments. Selfless healthcare and essential workers, serving the public at great personal risk. And, at the forefront of the crisis, a community of scientists equipped with a modern arsenal of genetic and immunological expertise and intent on the rapid evisceration of this disease. Thus, as the world awaits the vaccines that could bring this pandemic to a halt, the public psyche has never been more focused on the topic of immunity. How effective is immunity to this virus? And how long does it last? A new paper published in the Journal of Infectious Diseases from the lab of Dr. Jesse Bloom, from the Basic Sciences Division at Fred Hutch, studied the immune response to SARS-CoV-2 infection over time to understand the durability of immunity, and what implications it may have for the future of the pandemic.

There are, fortunately, clear indications that exposure to SARS-CoV-2, by infection or vaccination, generates some degree of protection from the virus in the form of immunity. And studies of other viruses provide an understanding of how immunity usually works. “For most acute viral infections, neutralizing antibodies [which defend our cells from pathogens] rapidly rise after infection owing to a burst of short-lived antibody-secreting cells and then decline from this peak before reaching a stable plateau that can be maintained for years to decades by long-lived plasma and memory B cells,” write the authors. But even after decades of study the immune system is notoriously unpredictable, raising the question of whether SARS-CoV-2 infection has the same effect. Thus, the Bloom lab teamed up with the University of Washington’s Dr. Helen Chu, whose work tracking viral respiratory infections in Seattle residents led to the first discovery of COVID-19 community transmission in the United States. Together, they studied how immunity evolves for several months following SARS-CoV-2 infection.

Using blood samples from COVID-19 patients, “we investigated the dynamics of neutralizing antibodies against SARS-CoV-2 in the three to four months following infection,” said Kate Crawford, a graduate student in the University of Washington Medical Student Training Program and lead author on the study. And, as with all research on this rampaging disease, haste was of the essence. “Thanks to [Dr. Chu and her team], we were able to get samples from individuals who were infected early in the pandemic. Thus, by mid-summer, we were already able to investigate antibody dynamics several months post-infection... it was exciting (although somewhat stressful) to be on the leading edge of figuring out these antibody dynamics,” said Crawford.  The authors found that the immune response to SARS-CoV-2 infection was similar to other viruses – for individuals across the disease severity spectrum, neutralizing antibody levels spiked in the first 30 days following infection, and then declined – but remained at substantial levels – over the next two to three months. The results offered no particular surprises, as Crawford reflected. “It’s fun and exciting to write papers about finding something you didn’t expect in science, but sometimes it’s just as important to publish the papers showing what you did expect and why you expected it.” In this tumultuous year, an unsurprising result has never been more welcome, especially when it suggests that the immune system is doing just what it is meant to do – generating a robust and, hopefully, durable response to protect from future infections by this virus.

While the results reported by the Bloom lab are promising, understanding how long this immune protection will last is a waiting game – we cannot know this until the immunity has worn off, and I think we can all agree that this is one scientific question for which we’ll all be happy to wait many years for an answer. In the meantime, Crawford has turned her attention to another means by which immunity may be lost, even in the continued presence of neutralizing antibodies. “My research is now focused on understanding the effects of mutations to the spike protein of SARS-CoV-2 [the protein that is recognized by neutralizing antibodies] and how mutations to spike might affect neutralization of the virus [by preventing antibodies from recognizing the mutated virus],” Crawford said.

Covid-19 immunity schematic

Crawford KHD, Dingens AS, Eguia R, Wolf CR, Wilcox N, Logue JK, Shuey K, Casto AM, Fiala B, Wrenn S, Pettie D, King NP, Greninger AL, Chu HY, Bloom JD. Dynamics of Neutralizing Antibody Titers in the Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection. The Journal of Infectious Diseases, 2020 Sep 30;  jiaa618.

This work was supported by the NIH/NIAID (grants R01AI141707 to J.D.B. and F30AI149928 to K.H.D.C.), the Bill & Melinda Gates Foundation (H.Y.C.; grant OPP1156262 to N.P.K.), the Burroughs Wellcome Fund (J.D.B.), and the Howard Hughes Medical Institute (J.D.B.).