Synflorix

Synflorix is the second pneumococcal conjugate vaccine to be used widely in Europe. It covers fewer serotypes than Prevenar 13 but has a peculiarity that deserves attention: its carrier protein comes from a different organism and brings a benefit of its own. This page explains the difference and puts into context what it means in practice.

What Synflorix is

Synflorix is a conjugate vaccine against ten serotypes of Streptococcus pneumoniae. As with all conjugate vaccines, the sugar capsules of the organisms are coupled to a carrier protein – only this makes them produce a robust immune response with memory in an infant.

What is special lies in the choice of this carrier protein. In most vaccines of this kind it is a detoxified diphtheria or tetanus toxin. In Synflorix, for eight of the ten serotypes, it is protein D, a surface protein of Haemophilus influenzae – and specifically of the strains without capsules, which cause middle ear infections in children. The remaining two serotypes are coupled to tetanus and diphtheria toxoid respectively.

From this arises the thinking behind the vaccine: the carrier protein is not merely a vehicle but an antigen in itself. A child that forms antibodies against protein D should in theory have gained something against the Haemophilus strains without capsules as well.

Important for context, because it is regularly misunderstood: Synflorix does not replace the Hib vaccination. That is directed against the encapsulated type b, which causes meningitis; protein D comes from the strains without capsules. They are different targets, and the Hib component of the six-in-one vaccination remains necessary.

Ten serotypes instead of thirteen

The obvious difference from Prevenar 13 is the coverage. Synflorix contains serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Missing are 3, 6A and 19A.

That is no small matter. Serotype 19A was the one that increased sharply after the introduction of the first seven-valent vaccine, frequently causes severe courses and is insensitive to several antibiotics. Serotype 3 is likewise associated with unfavourable courses.

Studies suggest that Synflorix has a degree of effect against 19A and 6A through cross reactions, because these types are related to types it contains. How strong this effect is is judged differently, and the evidence is less unambiguous than with direct coverage.

This weighing-up – wider coverage against a possible additional benefit for the middle ear – has been decided differently by different countries. Some immunisation programmes opted for Synflorix, others for Prevenar 13. The question has since largely settled itself, because vaccines with fifteen and twenty serotypes are available and programmes are switching to them.

In Austria the choice follows the immunisation schedule currently in force. Which vaccine is used for your child will be told to you by the paediatrician at the appointment – and the entry in the vaccination record sets it down.

The benefit for the middle ear

Middle ear infections are the commonest illness of early childhood and the commonest reason for prescribing antibiotics to children. A vaccine that reduced their number would be of considerable practical value.

The hope rests on a predecessor study from the early 2000s in which a vaccine with a protein D carrier reduced the number of middle ear infections due to the covered pneumococcal types and additionally due to Haemophilus strains without capsules – the latter by about a third.

Later studies under everyday conditions turned out more restrained. The total number of middle ear infections fell only moderately, because numerous other organisms cause the same illness and move in. The effect is there but smaller than had been hoped.

This assessment is part of honest advice. No pneumococcal vaccine turns a child into a child without earache. What all these vaccines prevent very reliably is the rare, severe, invasive disease – blood poisoning and meningitis.

What serotypes actually are

The term appears dozens of times on this page and in every pneumococcal recommendation and is rarely explained.

Streptococcus pneumoniae is a bacterial species. Within this species the strains differ in the chemical composition of their sugar capsule – and because it is precisely this capsule that the immune system recognises, every variant is something separate as far as the defences are concerned. More than ninety such variants have been described; they are called serotypes because they can be distinguished from one another with antisera.

In practice this means three things. Having had the illness protects only against the serotype concerned, not against the others – you can get pneumococcal disease more than once. A vaccine protects only against the types it contains. And the composition of a vaccine is a matter of selection, depending on which types caused most serious illness at the time it was developed.

The distribution is uneven and differs by region. A small proportion of the types causes most invasive disease – and which ones those are differs between Europe, North America and Asia. That is one of the reasons why there is more than one vaccine and why the recommendations are not identical worldwide.

With other organisms it is similar. With meningococci the variants are called serogroups and are designated with letters; with HPV one speaks of types with numbers. The principle is the same: one species, many variants, and a vaccination covering a selection of them.

The schedule

Like all pneumococcal conjugate vaccines, Synflorix is given in Austria in the third and fifth month of life and between the twelfth and the fourteenth – at the same appointments as the six-in-one vaccination, into the other thigh.

For premature babies and children at increased risk a schedule with an additional dose is used, because in them the response to two doses is less reliable. The calculation follows actual age, not the calculated due date – a child born two months early therefore also gets its first dose in the third month of life.

Synflorix is licensed up to the fifth birthday. Unlike Prevenar 13 it has no licence for adults – where an adult is to be vaccinated, with chronic illness or a missing spleen for instance, other preparations are used; see pneumococcal disease.

If a series has been started with one vaccine and it is no longer available, it is continued with another conjugate vaccine. That is permissible and usual; starting again is not necessary. Specialists speak of a mixed schedule, and it is expressly provided for with pneumococcal conjugate vaccines.

Tolerability

The commonest reactions correspond to those of other conjugate vaccines: redness, swelling and tenderness on the thigh, together with fever, restlessness, reduced appetite, sleepiness or increased crying for one to two days.

If the six-in-one vaccination is given at the same time, fever occurs somewhat more often than with separate appointments. This is known and accepted, because separate appointments mean more strain overall.

Lowering fever preventively is not recommended: it damps down the response to the vaccination slightly without any benefit arising. If the child is suffering from the fever, it is of course treated.

What belongs with a doctor: fever above 39.5 degrees, fever lasting more than 48 hours, a seizure, unusually shrill crying over hours or marked swelling of the whole leg.

The vaccination is not given where there has been a documented severe allergic reaction to one of its components. An acute febrile illness leads to postponement; a cold without fever does not.

How vaccines are compared with one another

That two vaccines cover different numbers of serotypes says little in itself. How a comparison comes about at all is worth explaining – it also explains why such questions are rarely answered unambiguously.

For a new pneumococcal vaccine no study is carried out today in which half the children remain unvaccinated. That would not be defensible, because an effective vaccine already exists. Instead the immune response is measured: does the new vaccine produce antibody levels corresponding to those of the established one?

This approach is necessary and has a weakness. Antibody levels are a surrogate measure. They say something about the immune response but not directly about illness prevented – and the threshold above which a level protects is itself a decision and not a constant of nature.

What actually counts only shows itself afterwards, in observing whole populations over years: how much invasive disease occurs, which serotypes circulate, whether something is shifting. These data come from national surveillance systems and not from licensing studies.

For advice a sober piece of information follows: anyone wanting to know which of the two vaccines is “better” will not get a simple number. Both produce robust immune responses against what they contain. The differences show themselves at the edges and over years.

What is in a dose of vaccine

Anyone reading the product information will find a fairly long list of components. It can be arranged in four groups, and each has a task.

The antigens – here the ten capsular sugars with their carrier proteins. That is what it is all about; the quantity is in the range of micrograms.

The adjuvant – an aluminium salt. Without it the immune system would hardly react to the purified components; more antigen and more doses would be needed. The quantity is below one milligram and thus far below what an infant takes in daily through food.

Stabilisers and salts – sodium chloride and water for injection, which ensure that the solution has the same salt concentration as the body and that the antigens remain stable.

Residues from manufacture in traces. They come from the production process and are largely removed; the remaining quantities are of no significance for people without a corresponding allergy.

Not contained are mercury compounds – today's single-dose vaccines in Europe need no preservative – and not contained are live organisms. A conjugate vaccine cannot cause pneumococcal disease.

Why there are competing vaccines at all

The question comes up regularly in consultations, and the answer is less mysterious than it sounds.

Vaccines are developed by companies, and a licensed vaccine from one manufacturer does not stop others developing one of their own. For health systems that is an advantage: competition brings prices down, and several manufacturers mean less dependence in the event of supply shortages – a subject that has gained importance in recent years.

For parents, on the other hand, it means confusion, because two preparations with different names fulfil the same task while not being identical. The useful information is this: both work very well against what they are directed at. The differences concern the edges – individual serotypes and a possible additional benefit – not the core.

Anyone who has a choice and wants to make it should discuss it with the paediatrician. In practice the vaccine used follows the immunisation programme and availability; a free choice rarely exists.

What this means for pregnant women

Directly, little – and that deserves saying, because this page is on a gynaecological website.

Synflorix is a vaccine for children up to the fifth birthday. It is not licensed for adults and is not used in pregnancy. Where a woman has an indication for a pneumococcal vaccination – asthma, diabetes, immune deficiency, a missing spleen – other preparations are used.

Indirectly the connection is there nonetheless. First, the question of which vaccinations are due in the first year of life belongs in the preparation for the birth – not in the exhausted weeks afterwards. Second, a newborn benefits from the herd effect: vaccinated small children carry pneumococci in the throat less often and pass them on less often, which counts especially for siblings in the household.

And third, the same applies to pneumococci as to many organisms in the first year of life: the child's vaccination begins in the third month. What protects before that is what is carried over from the mother – which with encapsulated bacteria is weak, because adults who have not been vaccinated hardly have high antibody levels against sugar capsules. A vaccine for pregnant women that would change this does not exist for pneumococci.

When a vaccine is withdrawn from the market

Synflorix is an example of a process that unsettles parents: a vaccine used for years disappears from the programme. It is worth knowing why that happens and what it does not mean.

The commonest reason is not a safety problem but a better alternative. When a vaccine with more serotypes becomes available and programmes switch to it, demand for the older one falls – and a preparation for which there is hardly any demand is eventually no longer manufactured. That is an economic and not a medical decision.

For children already vaccinated with the old vaccine nothing follows from it. The protection built up remains. A series that has been started is continued with the new preparation, and repeating the doses already given is not necessary.

The second reason for a disappearance is supply shortages, which have become commoner in recent years. They affect vaccines as they do other medicines and have to do with production chains concentrated in few locations. In such cases a temporary switch is made, and here too the rule holds: series are continued, not begun again.

What happens next

The child's vaccinations are given by the paediatrician. In this practice it is about what comes before: the dTpa and influenza vaccinations in pregnancy, the hepatitis B test, rubella protection – and the question of whether you yourself have an indication for a pneumococcal vaccination. Arranging an appointment.

If you would like an overview of the first year of life before the birth, it is on the page immunisation schedule for infants and small children. Comparing the appointments there with your own calendar while there is still peace to do so saves more effort in the first months than you would suppose.