Do Antibodies Equal Protection? They Don’t Know.

“We do have tests to measure antibodies. In theory, you could even measure virus, neutralizing antibodies in a specialty lab, but that’s not easy to do in a high-throughput way. We do not have what we call a true correlate of protection. We do not have a blood test or even a series of blood tests that we can say definitively, you know, thumbs-up, thumbs-down, you’re protected or not.”

Dr. Peter Hotez, co-director of the Center for Vaccine Development at Texas Children’s Hospital

https://www.yahoo.com/news/where-does-natural-immunity-stand-in-fight-over-vaccine-mandates-231039244.html

How many antibodies equals protection/immunity? If you are vaccinated but have low or no detectable antibodies, did the vaccine not work? What about if you are vaccinated and still got sick despite high levels of antibodies? If you have too many antibodies, does that mean you have an autoimmune disease due to an overactive immune system? If you have too few antibodies, do you have a weakened immune system?

The answer to all of these questions: THEY DON’T KNOW.

Take, for instance, the amount of antibodies present in a person. Do high or low antibody levels mean protection or rather an overactive or weakened immune system? Maybe…maybe not. It depends:

“If your immunoglobulin level is high, it might be caused by:

• Allergies
• Chronic infections
• An autoimmune disorder that makes your immune system overreact, such as rheumatoid arthritis, lupus, or celiac disease
• Liver disease
• Inflammatory bowel disease
• Cancer, such as multiple myeloma, lymphoma, or leukemia

Low levels of immunoglobulins mean your immune system isn’t working as well as it should. This can be caused by:

• Medicines that weaken your immune system, such as steroids
• Diabetes complications
• Kidney disease or kidney failure
• A weakened immune system that you were born with or developed (as with HIV/AIDS)

Just because your immunoglobulin level is high or low doesn’t mean you have one of these conditions.

Each person’s test can differ based on the method the lab uses to check the results. Talk to your doctor about your test results, and find out what you should do next.”

https://www.webmd.com/a-to-z-guides/immunoglobulin-test

THEY DON’T KNOW.

Do antibodies equal protection from Covid-19? These highlights are from antibody guidelines for the immunocompromised but they are very revealing in regards to the lack of knowledge about antibodies in general:

Antibody Testing After Getting the COVID-19 Vaccine: What to Know If You’re Immunocompromised

“The risk [for immunocompromised patients] is that you may be operating under the false belief that you’re protected, and you might not be,” says rheumatologist Jeffrey Curtis, MD, MPH, a Professor of Medicine at the University of Alabama at Birmingham who led the task force that created the ACR COVID-19 Vaccine Clinical Guidance. “But if an antibody test comes back with a certain number, nobody knows what that means.”

In other words, if an antibody test result were to indicate that you had antibodies after the COVID-19 vaccine, that doesn’t mean you can assume you’re fully protected. “If you adopt less preventive health measures as a result, that’s a risk,” says Dr. Curtis.”

“In other words, if an antibody test result were to indicate that you had antibodies after the COVID-19 vaccine, that doesn’t mean you can assume you’re fully protected.”

“Experts are still studying the effect of neutralizing antibodies for SARS-CoV-2 in humans. That means your doctor will not be able to tell you what your results mean in terms of your COVID-19 risk, since it’s not yet known what level of neutralizing antibodies would be needed to prevent infection in your body.“

“Because we don’t yet know what level of antibodies are correlated with COVID-19 protection, neither a “positive” qualitative or “high” quantitative test can tell you for sure if you’re adequately protected or not.”

You Can’t Draw Conclusions from Antibody Results

“First of all, no guide currently exists to translate the results of an antibody test for what it means for your protection from COVID-19.

“At this point, we don’t know how antibody presence or levels correlate with immunity well enough to say,” says Dr. Ramirez. “For some vaccines that have been in use for a much longer period of time, we have a better idea of which antibody levels correlate with protection.”

“What will be more common than receiving zero antibodies on your test: Your antibody level will be a certain number, whether low or high, but you won’t know if that’s a level that means you’re actually protected. “Nobody knows that for healthy people, and nobody knows that for immunocompromised people,” adds Dr. Curtis.”

“Given the difficulties with interpreting antibody tests, and that we do not yet know if a specific antibody level post-vaccination can predict protection, it would be difficult to make definitive conclusions,” says Dr. Ramirez.

Antibody Testing After Getting the COVID-19 Vaccine: What to Know If You’re Immunocompromised

THEY DON’T KNOW.

How do antibody levels relate to protection in regards to other “viruses” and vaccines? Some have high antibody levels, some have low levels. Some are protected, others are not. It depends:

Heterogeneity and longevity of antibody memory to viruses and vaccines

“Antibody levels to different vaccine and virus antigens were measured by their ELISA titer and normalized to the threshold of protection. The thresholds for protection were taken from the literature, and there are different standards for the protection to different infections [26,27]. We calculated the time for antibody titers to fall to the defined threshold for protection for the given vaccine or virus antigen. Due to a lack of data, we were not able to determine the consequences of variation in the threshold for protection between individuals. Different levels of immunity are required for different types of protection [27–30]. For example, higher levels of antibodies might be required to prevent infection, whereas lower levels of antibodies may not prevent infection per se but may still ameliorate disease or protect against lethal infection.“

“We examined the heterogeneity in both the magnitude and decay rate of antibody responses to different virus and vaccine antigens and used simple models to quantify how this heterogeneity affected the duration of protective immunity to a panel of vaccines and viruses. We found that variation in magnitude and decay rates of responses contribute comparably to the differences in antibody titers, that some individuals tend to make higher responses and these individuals also tend to have slower decay rates, and that different patterns of duration of protective levels of antibodies were elicited by replicating viruses and proteins.”

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006601

THEY DON’T KNOW.

To further illustrate the point that they do not know at what level or even if antibodies provide protection, here is a study on Mumps and antibody “protection” from 2015:

Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic

“Although it was assumed that mumps vaccination induces life-long protection, several mumps outbreaks, especially among vaccinated student populations, have been reported during the last decade in various countries where mumps vaccination has been implemented into their national immunization programs. In 2009-2012, a mumps epidemic (genotype G) arose that spread across multiple locations within the Netherlands, in which also primarily vaccinated students were affected. Waning of vaccine-induced immunity has been suggested to play a role in these outbreaks. When compared to the other components in the MMR vaccine, the mumps component seemed to be the least effective in eliciting good (high avidity) antibody responses, which were shown to wane to lower levels and in avidity index twenty years after a second MMR vaccination.”

“Yet our understanding of the natural serologic response against the mumps virus remains incomplete. Insight is into the ranges in mumps-specific antibody concentrations, their virus-neutralization capacity, as well as in the antibody dynamics seen in time after mumps virus exposure is lacking. The recent epidemic of the Netherlands provided an opportunity to evaluate such aspects of the antibody response following a clinical mumps virus infection. The course of anti-mumps IgG and virus-neutralizing (VN) antibody concentrations in 23 clinical mumps cases was investigated, 1-2 months and 7-10 months after onset of disease. Seven of these cases were not MMR vaccinated, which made it possible to investigate the difference in the course of antibody response between MMR vaccinated and unvaccinated persons after recent mumps virus infection. In addition, a control group was included in the study, to be able to represent the lower range of anti-mumps antibody levels as can be expected in healthy (non-infected) vaccinees that were age–matched.”

Discussion

“In the Netherlands, a high overall MMR vaccination coverage of 96% and 93% for respectively the first and second dose at 14 months- and 9 years-aged children has been reported. In a large cross-sectional cohort (n=7900) of the Dutch population (2006-2007), it was demonstrated that mumps seroprevalence appeared to be 91%, thereby reaching the herd immunity threshold of 86-92% (i.e. threshold percentages of mumps herd immunity combined from two studies, 86–88%22 and 88–92%23). A moderate reduction in seroprevalence, i.e. below or approaching the herd immunity threshold, was observed in several age groups, including the (vaccinated) age group of 15-21 years. The relatively low mumps-specific serum antibody levels in 15-21 year-aged persons confirm the vulnerability of this group with respect to mumps virus infection, and may explain the occurrence of the recent epidemic in the Netherlands (2009-2012), five years after this seroprevalence study. This epidemic has been described to count a total of 1,254 laboratory-confirmed mumps cases. The majority of the mumps cases was male (59%), university student (47%), 18-25 years of age (68%), and vaccinated twice with the MMR vaccine (68%). In the present study, two clear response patterns in IgG and VN antibody levels against the mumps vaccine strain could be detected in consecutive blood samples obtained from mumps virus infected persons during this epidemic. In previously vaccinated mumps cases, specific IgG concentrations as well as the ND50 values were significantly higher shortly (1-2 months) after onset of disease than at 7-10 months. This pattern in antibody response characterizes a secondary response, i.e. rapid production of antibodies upon subsequent encounter with the same antigen. Alternatively, unvaccinated mumps cases also mounted a seroresponse, but of generally lower IgG antibody concentrations and ND50 values at both sampling points than cases who had received 2 MMR vaccine doses. The overall IgG concentrations or ND50 values of the unvaccinated cases did not differ significantly between the two time points, and two out of the seven unvaccinated mumps cases had a lower IgG antibody response 1-2 months compared with 7-10 months after onset of disease. This antibody pattern is illustrative of a primary response. It is striking that four out of the seven unvaccinated mumps cases were aged ≥ 40 years, and it is likely, although not certain, that these persons had encountered wild-type mumps virus earlier in life. However, although natural infection with mumps is thought to confer lifelong protection, incidentally cases of reinfections have been described, and with the absence of circulating wild-type mumps virus also naturally-acquired immunity against mumps may diminish. In addition, it must be kept in mind that in our assays antibodies were measured against the mumps vaccine strain, which may result in a relatively lower response in persons with naturally-acquired immunity induced by other mumps virus strain(s). One of the two persons who showed a rise in mumps-specific IgG antibody level in time, suggestive of a primary response, was aged > 50 years, but the observed virus-neutralizing (VN) antibody response of this particular person was not typical for a primary response.“

The study design, i.e. observational study with limited sample size, did not allow determination of why mumps cases became infected despite vaccination. Recently, Gouma et al calculated a provisional cutoff level for protection of mumps-specific IgG of 243 RU/mL to discriminate between the pre-outbreak IgG concentrations from infected and non-infected persons in a large longitudinal serological database of students over the years 2009-2012. Vaccinated mumps cases in our study might have had pre-exposure levels below this cutoff value, based on the IgG antibody concentrations of the control group. Notwithstanding its limited sample size, our present study describes how mumps-specific antibody concentrations and their virus-neutralization capacity develop in time after mumps virus infection; the antibody response was significantly higher in the vaccinated mumps cases compared to the unvaccinated cases at both sampling times, suggestive of a better and more prolonged immunity against mumps. Although the humoral response certainly plays a role in protection against mumps, it should be considered that in vitro measured VN antibody concentrations, but also IgG concentrations, may not be fully predictive of immunological antibody activity in vivo, given that Fc-mediated phagocytosis, antibody-dependent cell-mediated cytotoxicity, and other processes that occur in the host are not reflected in the corresponding assays. Additionally, other immune mechanisms, such as cellular immunity, are likely involved in the protection against mumps disease as well as in the viral clearance. The cellular immunity against mumps has only been scarcely explored and deserves more attention.

Summarizing, mumps patients developed high levels of both mumps-specific IgG concentrations and mumps VN antibodies; vaccinated patients had higher antibody levels than unvaccinated patients. Antibody dynamics of vaccinated versus unvaccinated mumps cases differed, i.e. vaccinated mumps cases had higher antibody levels 1-2 months after onset of disease that declined at 7-10 months, which is characteristic of a secondary response. Previous MMR vaccination resulted in higher (functional) antibody levels in the mumps cases, probably by pre-existing B cell memory, although it was not effective enough to prevent mumps virus infection.“

“Seven out of the 23 mumps cases were unvaccinated and 16 cases were previously vaccinated with two doses of the MMR vaccine. In addition, 20 healthy control persons (25 yrs (22-29 yrs; 35% male) were included who had no symptoms of mumps or evidence of recent mumps virus infection based on serologic data. Two out of the 20 healthy controls (aged 55 and 57 years) were unvaccinated, and 18 controls were previously vaccinated with two doses of the MMR vaccine.“

Mumps-specific IgG concentrations were analyzed using the mumps vaccine strain (Jeryl Lynn (JL)) as antigen. The fluorescent bead-based multiplex immunoassay (MIA) using Luminex technology was performed as described before. Briefly, plasma samples were diluted 1/200 and 1/4,000 in phosphate buffered saline containing 0.1% Tween 20 and 3% bovine serum albumin.“

“Mumps virus-neutralizing (VN) antibodies were detected by focus reduction neutralization test (FRNT), partly based on the protocol described by Vaidya et al.34 Mumps vaccine virus (JL strain; stored at -80°C) was thawed and mixed with heat-inactivated (45 min 56°C) plasma samples (both 37.5 µl) to be incubated for 2 hours at 37°C. Culture medium (Dulbecco’s modified eagle medium (Life Technologies) supplemented with 5% fetal calf serum, penicillin, streptomycin, and L-glutamine) was removed from Vero cells (2 x 104 cells/mL) and 50 µl of virus/plasma mixture was added to each well of a 96 wells plate (i.e. > 20 plaques mumps virus per well). Plates were incubated for 4 hours at 36°C, wells were emptied and 200 µl of 0.8% carboxymethylcellulose medium was added to each well. Plates were incubated for 40 hours at 36°C with 5% CO2, before they were washed with PBS and subsequently fixed with a mixture of aceton and methanol (2:3). After 10 min, plates were washed with ice-cold PBS, and incubated with block buffer (PBS containing 1% BSA) for 30 min at 36°C. Anti-mumps nucleoprotein antibody (Abcam) was in block buffer (1:3000) and 100 µl was added to each well. After incubation for 1 hour at 36°C, plates were washed with PBS containing 0.1% Tween-20 (PBST). Subsequently, 100 µl of goat-anti-mouse IgG-HRP (DAKO) in block buffer (1:2000) was added to each well and plates were incubated for one hour at 36°C. Plates were washed with PBST and wells were stained with 50 µl of True Blue peroxidase substrate (KPL, Inc.). The numbers of plaques were counted and the 50% VN antibody dose (ND50) of each sample was calculated. The WHO international standard RubI-1-94 (NIBSC) was used as positive control in each assay run and to calculate relative ND50 value in order to adjust for inter-assay differences.“

doi: 10.1080/21645515.2015.1040967

In Summary:

• There is no true correlate of protection with antibodies nor a test that can definitively tell when one is protected or not
• Immunoglobulin levels being high or low can be caused by many conditions, however, having high or low immunoglobulin levels does not mean one has any of these conditions
• Each person’s test can differ based on the method the lab uses to check the results
• If an antibody test result were to indicate that you had antibodies after the “COVID-19′ vaccine, that doesn’t mean you can assume you’re fully protected
• Your doctor will not be able to tell you what your results mean in terms of your “COVID-19” risk, since it’s not yet known what level of neutralizing antibodies would be needed to prevent infection in your body
• They don’t yet know what level of antibodies are correlated with “COVID-19” protection
• You can’t draw conclusions from antibody results
• No guide currently exists to translate the results of an antibody test for what it means for your protection from “COVID-19”
• Whether low or high you won’t know if that’s a level that means you’re actually protected
• “Nobody knows that for healthy people, and nobody knows that for immunocompromised people,” according to Dr. Curtis
• Given the difficulties with interpreting antibody tests, and that they do not yet know if a specific antibody level post-vaccination can predict protection, it would be difficult to make definitive conclusions
• A study on antibody heterogeneity stated that the thresholds for protection were taken from the literature, and there are different standards for the protection to different infections
• Due to a lack of data, researchers were not able to determine the consequences of variation in the threshold for protection between individuals
• Different levels of immunity are required for different types of protection
• Higher levels of antibodies might be required to prevent infection, whereas lower levels of antibodies may not prevent infection per se but may still ameliorate disease or protect against lethal infection
• It was determined that variation in magnitude and decay rates of responses contribute comparably to the differences in antibody titers
• Different patterns of duration of protective levels of antibodies were elicited by replicating “viruses” and proteins
• A study on the mumps vaccine admits it was ASSUMED mumps vaccination led to life-long immunity
• This assumption has been challenged by several mumps outbreaks in highly vaccinated populations among those who have received 2 doses of the MMR vaccine
• Vaccinated students were primarily affected
• They presume waning vaccine-induced immunity/antibody levels are at fault
• The mumps component of the MMR seemed to be the least effective at eliciting high antibody response
• They admit that the knowledge of the serologic response to mumps remains incomplete
• They looked at 23 mumps cases, 7 of which were not vaccinated with MMR while the rest were
• A “control” group of healthy vaccinated individuals were included to show low-level antibody protection
• The Dutch population had reached the 91% vaccination threshold for “herd immunity” yet were still experiencing outbreaks among the vaccinated
• Low levels of antibodies in the 15-21 year-old age group meant they were vulnerable even with the “herd immunity” threshold achieved
• The majority (68%) of the mumps cases were among those vaccinated with the MMR vaccine 2x
• Vaccinated mumps cases had higher antibody levels than the unvaccinated
• 4 of the 7 unvaccinated mumps cases were above 40 years of age which SUGGESTED they encountered mumps earlier in life
• While natural infection with mumps is supposed to confer lifelong immunity, they admit reinfections do occur
• Antibodies in this study were measured against the VACCINE strain
• An over 50 unvaccinated individual had a IgG response suggestive of a primary response but the neutralizing antibody response was not suggestive of a primary response
• The limited sample size did not allow for them to determine why mumps cases occurred in the vaccinated
• The higher antibody response in the vaccinated mumps cases were SUGGESTIVE of a better immune response than the unvaccinated group
• However, they admit that results from experiments done IN VITRO (outside the body) do not necessarily equate to what actually occurs immunologically IN VIVO (in the body)
• They admit cellular immunity against mumps is scarcely explored and needs further research
• They conclude that previous MMR vaccination resulted in higher antibody levels but this did not offer protection against mumps

In other words: THEY DON’T KNOW.