Who Knew Drugs could have Antibodies

Is the 60-year battle to conquer the Respiratory Syncytial Virus (RSV) in its final phases?
Is bronchiolitis about to be banished for ever?  The propaganda might lead you to think so.

Most developed countries from USA to Australia and Luxembourg to Nicaragua have jumped on the bandwagon and give “free” immunisations with either Pfizer’s maternal Abrysvo, given to pregnant mothers, or AstraZeneca-Sanofi’s monoclonal antibody Beyfortus, given to newborn infants. These countries do not need RSV prevention – 97% of infant RSV deaths occur in low-income countries in Africa and India.

Do the benefits of these products outweigh the disadvantages?  What do we know about immunity and the response to RSV vaccines?

“Neutralising antibody” (NABs) concentrations can be measured in blood by seeing what concentration of serum neutralises 50% of RSV particles. As different researchers use different tests, measurements may not be directly comparable. But more importantly, how relevant are NABs to immunity?

In healthy adults, RSV NAB levels vary by a factor of 2, probably reflecting the time elapsed since our last RSV infection. Vaccinating not so young adults (over-60) with Abrysvo raises increases NAB levels 15-fold.

According to Astra-Zeneca Sanofi, 25% of newborn babies have no NABs “leaving them particularly Susceptible to RSV infection during their first RSV season.”  Happily a shot of Beyfortus on the day they are born can remedy this antibody “deficiency”.

Most babies (75%) have RSV NABs at birth. These naturally occurring NABs fall by 95% during the first year of life during which time all infants get RSV.

The NAB concentrations found in babies born to mothers given Abrysvo while pregnant are 11 times higher than normal. These are pharmacological (abnormal) rather than physiological (normal) levels. Do they give any protection?

The target for both Abrysvo and Beyfortus is the RSV F protein. Antibodies to this protein naturally vary 1000-fold in newborns, which might suggest RSV F is irrelevant.

A Recent Study suggests many infants exposed to RSV during the third trimester of pregnancy are protected but this protection does not stem from NABs.

How much do the RSV antibodies researchers measure have to do with the disease?  Is this why 50 years of attempts to find a vaccine for this usually harmless bug have got nowhere?

Good and Bad Antibodies

Most of us know that when we become immune to some infections we also develop antibodies. German Measles is a good example: both the virus and the vaccine can lead to what gets called protective levels of antibodies in blood.  But do we hear so much about antibodies because they can be easily measured by regulators and companies?

The Covid pandemic threw up claims that vaccine induced immunity was better than natural immunity and FDA and CDC began approving vaccines, in some cases mandated, on the basis of antibody levels.  We may now be seeing an attempt to row back from this – An Evidence-Based Approach to Covid-19 Vaccination.

One of the complications of an antibody approach is that just as the body can make antibodies to a germ, it can make antibodies against a medicine. Antibodies can attack penicillin and cause allergic reactions, which mean you have to avoid the drug completely. This is more difficult when a drug has been shown to be effective and needs to be taken long term or has a long half-life.

Eprex (erythropoetin alfa) is a hormone used to treat anaemic patients suffering from kidney failure. the kidney is the normal source for erythropoietin. Eprex stimulates bone marrow to produce red cells. But Anti-Drug Antibodies (ADA) to Eprex can attack the bone marrow cells making red blood cells and make patients very anaemic.

Monoclonal antibodies (MABs) are made in laboratories to attack specific body proteins. They came on stream in the 1990s. They are proteins which means they have to be administered by injection.

MABs like Humira were developed to treat inflammation in Crohn’s disease and rheumatoid arthritis but may also help with multiple sclerosis and now some cancers.  Humira became the best-selling drug in the world when its use was extended to minor inflammations like minimal psoriasis.  See Letter to Stacey London.

MABs seem particularly prone to triggering ADA, which may seem bizarre. The problem is common enough for FDA in 2019 to draw attention to the risks of developing ADA.  What risks?  We don’t know.

Theoretically antibodies will stop a MAB from working as well. ADA has been documented for all RSV MABs. Merck have a new RSV MAB Clesrovimab. In trials two-thirds of full-term babies developed ADA to it.

FDA make it clear that no-one knows what else might happen.  One of the worries is DRESS – Drug Reaction with Eosinophilia and Systemic Symptoms.  This is like a slow motion anaphylactic reaction to Penicillin or peanuts.  It can be fatal.  See No Way to Treat a Lady. And All Dressed Up Nowhere to Go.

MABs targeted to lower Eosinophil counts are a possible treatment for DRESS, but the same MABs can cause DRESS.

Many psychotropic medications like lamotrigine or antibiotics like minocycline can also cause DRESS and variations on it such as potentially lethal skin conditions like Stevens-Johnson Syndrome or Eosinophilic Esophagitis (our esophagus is continuous with our skin).

RSV MABs

The first MAB to be approved for RSV back in 1998 was palivizumab. This was given to preterm and other at-risk babies. Its disadvantage is that it has to be given by monthly injection. It seemed to prevent RSV in this small proportion of babies but it did not prevent infant deaths or actually treat the disease.

Nirsevimab (Beyfortus) appeared after the patent on palivizumab ran out. One shot is claimed to give a baby six months’ protection. Compared to palivizumab in an RCT of at-risk babies, there were more deaths on nirsevimab.

Despite this, Beyfortus is being rolled out all over the world – except the UK.

Newborn babies under 5 kg routinely have 0.5 ml of liquid containing 50mg of Beyfortus injected into their thigh muscles.  One month after the injection average NAB activity is 149 times greater than that at baseline.

These results are from clinical trials in babies averaging 3 months of age. We don’t know what happens to newborns, whose metabolism is different. By comparison a Vitamin K injection routinely given to newborns is a mere 1mg in 0.1 ml of liquid. (A 50 mg dose a large amount for an infant).

By now, almost June, if Abrysvo or Beyfortus given to manage the winter RSV season worked, we should have empty pediatric wards and bored doctors and nurses.

In the UK (Abrysvo territory) children’s hospital admissions due to RSV last winter cannot be said to have fallen when compared to the previous few years (dark blue line below).

In France, where Beyfortus is de rigueur, babies 6-11 months of age, immunised in the previous winter, are more likely to find themselves in intensive care units with bronchiolitis. Black line below (data up to 5 Feb 2025).

The majority (73%) of under-2s admitted to the intensive care unit with bronchiolitis in France were under 6 months of age, and the bronchiolitis was due to RSV in 62% of cases.

Beyfortus was given to 36% of these cases – leading to claims this shows a reduction of RSV infection admissions.  But the increased PICU admissions might stem from more children developing infections caused by other viruses (e.g. hMPV, rhinovirus etc.). RSV, hMPV and other cold viruses are paramyxoviruses.  An infection with one confers immunity to the others.  Another possibility is that massive antibody levels make false negative RSV results more likely.

Data from Galicia, where neonatal Beyfortus has been the norm for two winters, show that Beyfortified babies who get RSV are as ill as the unimmunised.

In addition to the problems infants have, A Shot in the Dark highlighted the preterm birth risk of maternal vaccination – the suggestion was poohpoohed.

However, a recent BMJ Open review of 6 RCTs and 2 observational studies of maternal RSV vaccination (involving over 20,000 births) confirmed the preterm birth association. The authors used a statistical approach that minimizes the risk but even with this their data point to a real problem.

From Japan, Med Check, edited by Dr Rokuro Hama, has also analysed the Abrysvo data and advises against its use, citing the preterm births, adverse maternal events including preeclampsia, and dubious efficacy in preventing bronchiolitis.

These products look over-rated.  What should prospective parents do?

The bottom line seems to be that the safety and efficacy of these products are still uncertain. Beyfortus in particular is breaking new ground being a massive dose of monoclonal antibodies – a class of drug never before injected into the newborn, without any prior safety testing in such young babies.

Breast feeding is effective at reducing RSV disease in children. It also seems likely that the more “colds” due to RSV women have before and during their pregnancies, the better their child will be protected. None of these new products have been shown to save lives.

So why are the relevant paediatric and obstetric professional organisations jumping on the bandwagon of whole-hearted support for these interventions when the grounds for doubts are so strong?

Infallible Papal Immunity

The late Pope Francis was wary about viral respiratory diseases, having had part of his lung removed as a youngster. During the Covid pandemic, he became the first Head of State to mandate the vaccines for all Vatican residents. Three members of the Swiss Guards that protect a Pope resigned

RSV vaccination is being pushed for the not so young. The guidelines recommend Abrysvo up to the age of 80.  Francis was 88 but was immunised, perhaps because he was visited by a pal – vaccine enthusiast Fernando Polack.

Frankie didn’t die from an RSV infection, but his doctors kept mentioning a complex respiratory state of affairs. Did Abrysvo make him more prone to hMPV, a rhinovirus or one of the other paramyxoviruses that seem to become more problematic after an RSV vaccine? This was a problem Moderna failed to solve with its mResvia vaccine which combined RSV and hMPV components – see The RSV Virus Challenge.

If Covid or the Flu don’t get you RSV will

The infection probably hasn’t spread to Europe or anywhere else just yet, but it’s pretty virulent in North America, where even the most skeptical and sensible of no-longer young folk (over 60 that is) who have a minor sniffle are now likely to engage with conversations about which of the potentially lethal infections – Covid, the Flu or RSV – they have.

Industry are rushing in to help with self-test kits.  The question can be settled.

But be warned, a positive test might lead to social isolation. You are very likely to be banned from seeing your grandchildren. Why didn’t you get the vaccine?  That will teach you.

Having a sniffle is harmless.  If you have a Covid, Flu or RSV sniffle, the Crucifix and garlic will be held up in front of you – you who have wantonly flouted social norms by not getting the treatment for your vaccine-preventable disorder.

Post by Peter Selley.  See Birth Defects Research Vaccines in Pregnancy