Resident Eagle: Antibody Response After the COVID-19 Vaccine, Part 3

Resident Eagle is an intermittent column that profiles the work of top EMS physicians and medical directors from the Metropolitan EMS Medical Directors Global Alliance (the "Eagles"), who represent America’s largest and key international cities. For information on the alliance, see useagles.org.

The first two installments of this column described a group of top EMS physicians’ research to determine percentages of neutralizing antibodies produced following receipt of the Pfizer-BioNTech COVID-19 vaccine in residents of a Florida assisted living facility and healthy young comparison cohort, as well as how long their protection lasted. They found that while second-dose protection waned, third vaccine doses were a “game-changer” that provided more lasting protection. Find those articles here:

• Part 1, How Long Will the COVID-19 Vaccine Protect You?
• Part 2, Antibody Response After the COVID-19 Vaccine

The conclusion of this 3-part series explores the implications of these results. 

Protection and Duration

In summary, point-of-care assays (POC) for identifying the presence of anti-COVID IgG and the respective percentage of neutralizing antibodies (Ab) were very useful tools.

Consistent with prior and subsequent investigations, these assays confirmed that escalating age and immunomodulating conditions (IMCs) affect the timing and degree of IgG production as well as the percentages of neutralizing antibodies (%nAb) developed after initial mRNA vaccination. 

These user-friendly POC devices also provided readily available indicators of protection as well as the duration of that protection for individuals while also demonstrating the progressive decline of %nAb post-dose 2 as an overall trend for most vaccinated persons.

While most adults under 90 likely had protective %nAb levels 3 weeks after dose 2, the data indicated that over time the %nAb for vaccinated adults falls to unsafe levels, even in healthy individuals under 50. The declining %nAb levels were an important signal that supported the need for additional or more concentrated doses, especially in elderly persons or those with IMCs. However, it predicted a decline of protection for most young, healthy adults as well as future determinations of likely vaccination needs.

Most important, the preliminary post-dose 3 data also indicate that third doses of vaccine lead to more profound and persistent %nAb levels and that the POC tests had great utility in that respect as well. While those findings give direct evidence of protection from humoral antibody response, they likely also reflect a much broader level of protection from other elements of the immunological response to COVID-19.

Neither of these 2 POC assay results were directly validated by traditional testing methods, and investigators  cannot directly attest to their absolute accuracy. However, both assays had remarkably consistent and reproducible results among individuals, and the findings are consistent with known immunological expectations related to age. The findings were also indirectly validated by other subsequent formal study results and CDC reports. The findings not only seemed to be well-corroborated in retrospect, but they made logical sense as well.

The takeaway is that the third dose of COVID-19 vaccination is profoundly important and should be strongly recommended to all. While the preliminary information does signal the subsequent need for fourth doses in most persons, that need is less urgent than it was prior to dose 3.

The authors wish to acknowledge Lauren Rosenberg; Maricar Cabral, RN, CCRN; Remle Crowe, PhD; Jonathan Jui, MD, MPH; Megan Marino, MD, FAAP; and Aileen Marty, MD.  

Table 1: Onset of Antibody Production After Initial Vaccination

• Paralleling the original Pfizer vaccine trial, by day 14 after dose 1, 27 of 39 persons (69%) who were less than 70 years of age had new Ab production.
• At the same time, no Ab were detected in 84% of the 38 persons older than 70. 
• By day 21, even before dose 2 was administered, 100% of those under 60 had become Ab-positive except 2 individuals with immunomodulating conditions (IMCs). 
• For each successive decade of age, a progressively smaller number of persons were Ab-positive (eg, only 20% of those older than 90). 
• On day 7 after second doses, 100% of those under 80 were Ab-positive (except the 2 with IMCs), as well as 89% in their 80s (n=18) and 78% if older than 90s (n=10). 
• 2 weeks later only 2 persons remained Ab-negative, 1 with an IMC and 1 who was 93 years old.
• Semiquantitative results (darker band versus a much lighter band on the lateral-flow chromatography cassette) indicated very strong Ab response in 100% of persons under 80 tested by day 42.
• The POC assay used had consistent and reproducible results.

Table 2: Magnitude and Duration of Neutralizing Antibodies After Second Doses

ALF Group

• Paralleling the qualitative (positive or negative) POC test results, at day 7 after dose 2, the average percentages of %nAb levels were 95%–99% in the ALF workers/residents who were in the 23–50 age groups.
• However, the average %nAb remained borderline or inadequate for those older than 70 or with IMCs. 
• By day 21 after dose 2, average %nAb levels had begun to elevate and rose to 91% for those ages 61–70, 75% for 71–80, and 55% for 81–90. 
• While the average percentage reflected relative trends, it portrayed the actual variation among individuals.
• Among the 8 persons older than 90, the average %nAb was 35%, but half still had no detectable nAb. 

Community Group

• The initial findings on days 7 and 21 after dose 2 in the community-based cohort of healthy individuals fully matched the ALF findings, with strong levels of neutralizing Ab found in those under 50 but progressively lower %nAb with increasing age.
• Nevertheless, even among those in the 30–70 age groups, the %nAb assay progressively declined from the 90%–95% range to much lower levels within the ensuing several months. 
• An interesting finding was that tested adolescents sustained relatively high levels of %nAb 6 months after dose 2 while most adults over 20 had borderline/inadequate levels at that same 180-day mark. 

Table 3: Striking Neutralizing Ab Responses Following Dose 3 of Vaccine

• In contrast to dose 2, with few exceptions, almost every tested adult had more than 99% nAb by day 21 after a third dose.
• Most important, those same optimal levels of nAb persisted at 100 days and 150 days, respectively. 
• For example, a 71-year-old man who had age-predicted modest levels of 68% nAb at 21 days after dose 2 fell to 55% at day 100, 42% at day 150, and 16% at day 180 post-dose 2.
• However, in contrast to dose 2, that same person had striking and markedly sustained elevations after dose 3.
• Versus the age-predicted 68% nAb found 21 days post dose 2, the %nAb rose from 16% (day 180 after dose 2) to 99.3% at day 21 after dose 3, with sustained levels of 99.2% at day 100 and 99.7% at day 150.
• Of important note here is that the initial 180-day results were only available from 2 persons at the time of publication (the first 2 reaching the 180-day mark post-dose 3), the previously mentioned 71-year-old and another 49-year-old. They still retained a robust percent of nAb at 92.7% and 89.6%, respectively. However, those 180-day numbers were definitely lower than the 99%-plus nAb observed for the first 5 months after dose 3.
• This first downward trend is nowhere near the rapid rate of decline seen after dose 2 but still bears watching and perhaps subsequent considerations for another (fourth) dose sometime in the near future.
• While these nAb responses only reflect one aspect of immunity from the original vaccine product, breakthrough infections may still occur, but clearly only with mild illness. 

Paul E. Pepe, MD, MPH, is coordinator of the Metropolitan EMS Medical Directors (aka “Eagles”) Global Alliance, Dallas, Texas.

Peter M. Antevy, MD, is EMS medical director for the Coral Springs-Parkland Fire Department and Davie Fire Rescue, Broward County, Florida.

Kenneth A. Scheppke, MD, is deputy secretary for health for the state of Florida. Prior to his appointment Scheppke served as the state EMS medical director and medical director for 7 fire-rescue agencies across Palm Beach and Martin counties.