Questioning Offit. Part 16. Antigens

Previous parts:
Part 1: Introduction
Part 2: DTP
Part 3: Encephalopathy
Part 4: Dravet syndrome
Part 5: SIDS
Part 6: West syndrome
Part 7: Hib
Part 8: Hepatitis B
Part 9: Pneumococcus and rotavirus
Part 10: HPV
Part 11: Lawsuits
Part 12: Wakefield
Part 13: MMR and autism
Part 14: Mercury and autism
Part 15: Chickenpox

“One of the painful things about our time is that those who feel certainty are stupid,
and those with any imagination and understanding are filled with doubt and indecision.”
—Bertrand Russell

Chapter 10. Dr. Bob

Offit devotes his tenth chapter to pediatrician Robert Sears, author of more than forty parenting books. In his 2007 book on vaccines, Sears proposes an alternative vaccination schedule that he considers safer.

“No reasonable parent can watch a child receive as many as five shots at one time and not worry it’s too much” - Offit writes, - “But the fear should be allayed by the science.”

Although the number of vaccines given to young children today is more than at any time in history, the immunological challenge from vaccines is lower. A hundred years ago, young children received one vaccine: smallpox. Today, they receive fourteen. But it’s not the number of vaccines that counts; it’s the number of immunological components contained in vaccines. Smallpox, the largest virus that infects mammals, contains two hundred viral proteins, all of which induce an immune response. Today’s fourteen vaccines are made using viral proteins, bacterial proteins, and the complex sugars (polysaccharides) that coat bacteria. Each of these components, like viral proteins in the smallpox vaccine, evokes an immune response. The total number of immunological components in today’s fourteen vaccines is about a hundred and sixty, fewer than the two hundred components in the only vaccine given more than a hundred years ago...
Arguably, a single infection with a common cold virus poses a much greater immunological challenge than all current vaccines combined.

The components that trigger an immune response are called antigens. As parental anxiety grew in the 1990s alongside the expanding childhood vaccination schedule, Offit published a paper in Pediatrics in 2002 titled “Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?” Instead of discussing vaccine ingredients such as aluminum or thimerosal, Offit reframes the issue. He argues that rather than counting adjuvants or preservatives, one should count only antigens.

In the article—which later became widely cited by researchers and journalists—Offit calculates that an infant could theoretically receive 10,000 vaccines at once without harm. He arrives at this number by taking the infant’s pool of B-lymphocytes, dividing it by the number of antigens in a vaccine, and concluding that 10,000 simultaneous vaccines would be entirely safe.

In contrast to the more restrained tone of his scientific paper, Offit raises the figure even further in his book, putting it at 100,000 vaccines. He writes:

Given the number of B cells in the bloodstream, the average number of epitopes contained in a vaccine, and the rapidity with which a sufficient quantity of antibodies could be made, babies could theoretically respond to about a hundred thousand vaccines at one time.
The model isn’t perfect. It assumes that the immune response is static, which it isn’t. Every minute new B cells generated in the bone marrow pour into the bloodstream. So, it would be fair to say that at any single point in time a child could theoretically respond to a hundred thousand vaccines.

No parent has ever claimed that the problem is the number of antigens. Parents were worried mainly about neurotoxic substances like mercury and aluminum, which can remain in the body for years when injected intramuscularly. Parents were alarmed by three or four live viruses being given to an infant at the same time. Some were concerned about other ingredients, such as polysorbate 80 or fetal cell lines. But the number of antigens was never the issue. Offit’s reframing has been used in many scientific papers ever since and became the core argument for the safety of combined and simultaneous vaccination.

From 2018 through August 2024, the CDC website listed 13 papers supporting the safety of giving vaccines at the same visit. All were written by CDC staff. At first glance the list looks substantial, but following the links shows something different. Of the 13 studies, four are duplicates. Why the CDC cites the same study twice is unclear. The most likely reason is to make the list look longer. Once the duplicates are removed, only nine unique publications remain. Here is a closer look at them:

1. Glanz 2015 is only a feasibility analysis. It looks at the VSD database (a closed database to which the CDC restricts outside access) and concludes that different children received different amounts of aluminum through vaccines, and that these groups could be compared. That is all. The study does not compare them. And even if it did, it would have no bearing on the question of giving vaccines simultaneously. Notably, ten years after publication, the study it proposed has still never been carried out.

2. Glanz 2016 is also not a study; it is merely a discussion of whether the safety of the full vaccination schedule can be compared with an alternative schedule using the VSD. The CDC authors conclude that yes, it can. But this study, too, has never been performed.

3. Daley 2018 examines how accurately parents report their children’s vaccination status. It has nothing to do with the safety or scheduling of combined vaccines.

4. Sukumaran 2018 looks at the effects of maternal vaccination on infants. It has nothing to do with giving multiple vaccines at the same time.

5. McCarthy 2017 compares mortality in children vaccinated according to the schedule with those who received at least one vaccine with delay. We’ll discuss this study in more detail later, but it also has no bearing on the safety of simultaneous vaccination.

Hence, of the 13 references, nine are either duplicates or completely unrelated to the topic.

6. Wang 2018 proposes a method for assessing the safety of giving vaccines at the same time without a control group. The authors use a self-controlled design, comparing seizure rates in the 7–10 days window after vaccination with rates in the 14–56 day window. This design cannot serve as proof that giving multiple vaccines at once is safe, because it relies on assumptions about the timing and nature of side effects that may be incorrect.

The remaining three papers—DeStefano 2013, Iqbal 2013, Glanz 2018—focus on antigen counts. They don’t compare the number of vaccines given, only the total number of antigens.

For example, Iqbal 2013 explicitly states: “Offit et al. suggested that taking into account the number of antibody-stimulating proteins and polysaccharides in vaccines might provide a better assessment of the level of immunologic stimulation rather than simply counting the number of vaccines received“. Offit suggested it, and the CDC adopted the idea without any evidence to support it. The actual questions—how many vaccines are given, or how many potentially toxic ingredients they contain—are neatly removed from consideration.

The CDC removed this embarrassing set of papers in 2024, and as of 2025 the only scientific source it cites to justify the safety of simultaneous vaccination is a 1994 Institute of Medicine report. According to the CDC, the report states that “it seems unlikely that the number of separate antigens contained in childhood vaccines ...would represent an appreciable added burden on the immune system that would be immunosuppressive.“ In the CDC’s view, that single line from a 30-year-old report is sufficient to establish the safety of giving multiple vaccines at the same visit.

Now back to McCarthy 2017, since the CDC included it. The study compares mortality in children vaccinated according to the schedule with mortality in those who received at least one vaccine later. It could have been a meaningful study, had the authors not excluded all deaths occurring before 19 months of age, as well as deaths from illnesses that began before 19 months. These categories account for most deaths. As a result, only 18 deaths remained across both groups, and no statistically solid conclusions could be drawn from numbers that small.

Among all the CDC’s cited sources, not a single study directly compares children who received two or more vaccines at the same visit with children who received only one. Such studies do exist, but the CDC does not mention them.

1. Israeli study, 2009. Side effects were reported in 57% of children who received MMR together with the pentavalent vaccine, but in only 40% of those who received MMR alone. The authors concluded that “it may be necessary to reconsider the current vaccination policy regarding concomitant injections.”

2. 2014 study from Guinea-Bissau. Children who received the pentavalent vaccine in addition to measles and yellow fever vaccines died almost eight times more often than children who did not receive the pentavalent vaccine.

3. Danish study, 2016. Getting MMR and the pentavalent vaccine at the same visit was linked to a 27% higher risk of hospitalization for lower respiratory infections compared with getting MMR alone.

4. 2007 study from Guinea-Bissau. Children who received DTP at the same visit as the measles vaccine had twice the mortality of children who received the measles vaccine alone. Similar findings were reported in Gambia, Malawi, Congo, Ghana, and Senegal.

5. 2012 VAERS analysis. Mortality among children who received 5-8 vaccines at the same visit was 1.5 times higher than among those who received 1-4 vaccines.

6. U.S. study, 2006. Infants who received a combination vaccine (DTaP + polio + hepatitis B) together with pneumococcal and Hib vaccines made emergency-department visits at twice the rate during the three days after vaccination compared with infants who received the vaccines separately. They were seven times more likely to undergo a sepsis work-up, ten times more likely to have a lumbar puncture, and three times more likely to be given antibiotics.

7. FDA study, 2024. Getting the COVID-19 and flu vaccines at the same visit was linked to a higher stroke risk in older adults. Another study found that giving these two vaccines together caused more side effects than giving them separately.

9. Indian study, 2011. After the switch from the three-component vaccine to the pentavalent vaccine, 24-hour post-vaccination mortality doubled.

10. German study, 2005. The authors examined mortality following two hexavalent vaccines (Infanrix Hexa and Hexavac). Among children in their second year of life, 24-hour mortality after Hexavac was 31 times higher than expected. The authors note that the number of SIDS cases occurring a few days after vaccination is likely underreported, because these cases are not consistently submitted to the Paul Ehrlich Institute (which collects vaccine-adverse-event reports). For example, of six SIDS cases that occurred within two weeks of a hexavalent vaccination, only one—the one that occurred within the first 24 hours—was reported.

11. German study, 2011. The fourth dose of a five- or six-component vaccine was associated with a 16-fold increase in SIDS risk, and any dose with a two-fold increase.

12. Large Italian study, 2011. SIDS risk during the first week after Hexavac was elevated 2.8-fold. SIDS risk after the first dose of any hexavalent vaccine was elevated 2.2-fold. SIDS risk during the week after any first vaccination was elevated 1.5-fold. This was a self-controlled study in which each infant served as his or her own control prior to vaccination and during the 14-day period afterward.

13. Italian study, 2014. Twelve percent of all SIDS cases occurred within one week of vaccination with hexavalent vaccines (Infanrix Hexa and Hexavac).

14. In 2011, GlaxoSmithKline (GSK) submitted a confidential report to regulators on sudden deaths occurring within 20 days of the hexavalent vaccine. The document was later released by an Italian court. The report claimed that the number of sudden deaths recorded after the vaccine did not exceed the background rate. But 90% of the deaths occurred within the first 7 days after vaccination. Even more striking, 97% occurred in the first 10 days, with only 3% in the following 10. In addition, 6 of the 8 sudden deaths in children in their second year of life occurred within the first 3 days after vaccination.

15. In 2015, GSK submitted another confidential report to European regulators. According to it, 52% of SIDS cases occurred within 3 days of vaccination and 82% within 7 days. After the first dose of a hexavalent vaccine, 98% of sudden deaths fell within the first 10 days and only 2% in the following 10. The manufacturer concluded the vaccine was safe, and the European Medicines Agency (EMA), responsible for vaccine safety oversight in Europe, accepted the report without further review.

***

Up to this point, the focus has been solely on safety. But there is also a substantial body of research showing that combination vaccines are less immunogenic and less effective than separate shots.

In a randomized trial in Germany, the standalone Hib vaccine generated a stronger antibody response than the combination vaccine. A Finnish randomized trial found the same. In a 1997 randomized study, the combination vaccine produced a markedly weaker immune response to both Hib and tetanus than giving the vaccines separately. A Cochrane systematic review confirmed these findings.

A 2000 randomized study showed that giving the Hib vaccine together with the inactivated polio vaccine resulted in far fewer Hib antibodies than giving Hib with the live polio vaccine. It was also found that when Hib and DTaP were given at the same visit as two separate injections in different sites, the tetanus antibody response was significantly reduced.

A 2003 study by the UK Health Protection Agency found that among children who developed Hib disease despite vaccination, the combination Hib + DTaP vaccine was nearly seven times less effective than the standalone Hib vaccine. After the UK switched to the acellular pertussis combination vaccine (Hib + DTaP), Hib cases rose almost sevenfold.

On one side, then, we have Offit’s theoretical B-cells calculations and his assumption that counting antigens gives a better sense of “immune load” than counting vaccines. On the other side, we have dozens of real-world studies showing that simultaneous vaccination and combination vaccines are less safe and less effective than separate shots. Offit and the CDC disregard these studies and rely instead on theoretical estimates.

In 2010, in response to the growing fear of so many vaccines given so early, researchers at the University of Louisville performed a study of more than a thousand children. They found that children who were vaccinated completely and on time were not more likely to suffer neurological problems than children whose parents had chosen to delay vaccination.

This study relied on the data from Thompson, 2007, which was already discussed in the “Mercury and Autism” part. The authors divided children into those fully vaccinated on time and those who were vaccinated with some delay. The group with the delayed vaccination received only slightly fewer vaccines in the first year of life (an average of 10.1) compared to the on-time group (an average of 11.8). In other words, the authors essentially compared fully vaccinated children with other fully vaccinated children who received some shots a bit later. Not much later—just a bit later.

Moreover, the children who were vaccinated a bit later came from poorer and less educated families. The authors compared neuropsychological scores between the two groups and found no differences, even though it would have been entirely reasonable to expect that the more affluent and educated group would score higher. The sample also included nine completely unvaccinated children, but the authors did not analyze them separately.

A similar 2013 study compared children fully vaccinated on schedule with under-vaccinated children. “Under-vaccinated” meant children who missed at least one vaccine or received at least one dose even a single day later than the recommended schedule. Children who were under-vaccinated by parental choice had 9% fewer emergency-department visits, 5% fewer doctor visits, and 11% fewer cases of pharyngitis and upper-respiratory infections.

Offit:

But despite the fact that the hepatitis B vaccine is given after exposure, almost all babies are protected. It is rather remarkable that following passage through a birth canal containing literally billions of hepatitis B viruses, a one-day-old baby can mount a protective immune response to a vaccine that contains only twenty micrograms (millionths of a gram) of one highly purified viral protein.

The fact that the hepatitis B vaccine triggers an immune response within the first day after birth does not mean that this schedule is more effective or safer than giving the vaccine at a later age. A 2018 study from India, where hepatitis B is widespread, found no difference in effectiveness between vaccination at birth and vaccination at six weeks. An Israeli study showed that in premature infants the hepatitis B vaccine produces a stronger immune response when given later.

We have already discussed the safety of administering the hepatitis B vaccine right after birth. Recall that, to declare it safe, the CDC had to assume that unvaccinated premature newborns weighing 1.3 kg have the same risk of death as vaccinated full-term infants weighing 3 kg.

Offit:

Sears advises, “It’s probably okay to give the combination MMR booster at age five, when a child’s immune system is more mature.” Because the MMR vaccine is recommended for children between twelve and fifteen months of age, Sears implies that a baby’s immune system isn’t mature enough to respond to vaccines. To the contrary, vaccines given in the first year of life induce an excellent immune response.

This is, to put it mildly, not the case. For example, a 2012 study reports that immune responses in infants are weaker and shorter in duration. Vaccine effectiveness in the first year of life, and especially in the first months, is very low. To generate and maintain an adequate B-cell immune response in infants, strong adjuvants and repeated booster doses are required. The problem with this approach is that repeated stimulation of the immune system with the same antigen plus an adjuvant can overcome genetic resistance to autoimmune reactions. This effect is confirmed by studies. For example, in a 2008 Canadian study, delaying the first DTP dose by only two months was associated with a twofold reduction in asthma risk.

In most countries the first measles vaccination is recommended at 12 months, even though its effectiveness is 3–4 times higher when given after 15 months. It is not administered before 12 months in most countries because in that age range it is practically ineffective. Therefore doses given to infants under 12 months during outbreaks or by mistake are not counted and are repeated after the child reaches 12 months.

Pertussis vaccination is very ineffective at 2/4/6 months because of the presence of maternal antibodies. This is why a 5-dose schedule is used in addition to maternal vaccination during pregnancy. And in children vaccinated against Haemophilus influenzae in infancy, antibody levels were significantly lower than in those vaccinated after one year of age.

In contrast to the unfounded claims of Offit and the CDC, virtually all existing studies show that combined vaccines are less safe and less effective than separate vaccines. This, of course, does not imply that the separate vaccines are safe or effective enough on their own, that question is addressed separately for each one of them.

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