Practical guidelines for vaccination of children with autoimmune diseases and treatment of various immunosuppressive programs

Autoimmune diseases include systemic and organ-specific autoimmune diseases, such as the digestive tract (inflammatory bowel disease), eyes (uveitis), skin (psoriasis) or central nervous system (multiple sclerosis) Disease)
.

These children receive immunosuppressive therapy to control the disease, which includes traditional immunomodulatory drugs such as glucocorticoids (GCs), disease-modifying anti-rheumatic drugs (DMARDs) and biological agents

Glucocorticoids (GCs), disease-modifying anti-rheumatic drugs (DMARDs) and biological agents

Upper respiratory tract infection is one of the most common infections.

Since most patients receive combination therapy rather than a single drug, it is particularly challenging to design a clinical study to evaluate the impact of various immunosuppressive regimens on the risk of infection and to understand the biological mechanisms behind the risk of infection
.

recommend:

recommend:

Vaccination with inactivated vaccine

Vaccination with inactivated vaccine

When a disease that may require immunosuppressive treatment is diagnosed, the child’s vaccine status should be verified
.

All inactivated vaccines can be vaccinated without restriction, but they should be vaccinated 2 weeks before the start of treatment to increase immunogenicity

Vaccination 2 weeks before the start of treatment to improve immunogenicity

Influenza vaccine recommendation

It is recommended that all children with immune-mediated diseases receive seasonal influenza vaccine every year , regardless of whether they are treated with immunosuppressive agents, because influenza can be very serious and increase the risk of secondary bacterial infections
.

In the first year, two doses are recommended for patients under the age of 9 who have never received the flu vaccine or have an unknown vaccination history

Vaccination of seasonal influenza vaccine, regardless of whether immunosuppressive therapy is used, two doses are recommended for patients under 9 years of age who have never received influenza vaccine or have unknown vaccination history

Hepatitis A vaccine recommendation

Hepatitis A vaccine should be provided to seronegative children with autoimmune diseases who frequently travel to endemic countries
.

The injection time should follow national guidelines

Serology to control the response of immunosuppressed children to hepatitis A virus

Hepatitis B vaccine recommendation

Hepatitis B vaccine recommendation

It is recommended that children with autoimmune diseases receive hepatitis B vaccine, because serious illnesses may occur during the period of immunosuppression
.

All children should undergo serological screening immediately after diagnosis

According to national guidelines, for children who are seronegative (without anti-HBs antibodies), hepatitis B should be vaccinated with three doses.

The maintenance of HBs antibodies in immunosuppressed children should be monitored regularly

Human papillomavirus (HPV) vaccine recommendation

According to the national vaccination schedule, it is recommended that young people aged 11-26 with autoimmune diseases receive HPV vaccine
.
The immunogenicity results of previous studies indicate that it may be useful to assess vaccine response and antibody persistence, although there is still no recognized cut-off value for seroprotection in this age group
.

It is recommended that young people aged 11-26 with autoimmune diseases receive HPV vaccine
.

Pneumococcal (PCV) vaccine recommendation

Pneumococcal (PCV) vaccine recommendation

   Many countries still recommend PCV13 and PPV23 pneumococcal vaccines, such as the United States, Canada, Cyprus, Greece, France and Spain
.
For example, the American Immunization Practice Advisory Committee recommends the following vaccination schedule for children with chronic diseases: four doses of PCV13 at 2, 4, 6, and 12-15 months of age, and then every 5 years between the ages of 2 and 18 Inoculate two doses of PPV23
.
The reason is that PPV23 increases the protection of more serotypes than PCV13
.
However, due to its T cell-dependent characteristics, it can only induce short-term immunity and an immune response weaker than PCV13, which is a T cell-dependent antigen
.
Therefore, only PCV13 is recommended in Switzerland
.
In general, conjugated pneumococcal vaccines should be more popular than polysaccharide vaccines, because conjugated vaccines can produce a higher affinity antibody response, a longer-lasting immune response, and the production of memory B cells
.
The booster vaccine combined with the vaccine can expand the memory B and T cell populations
.
On the contrary, boosting common polysaccharide vaccines may deplete the memory B cell pool because of the lack of memory cell induction
.
Some countries still include polysaccharide vaccines in their recommendations.
This fact depends on the distribution of pneumococcal serotypes circulating in the country
.

The reason is that PPV23 increases the protection of more serotypes than PCV13

  According to the National Immunization Guidelines, it is recommended that all children with autoimmune diseases receive pneumococcal vaccine
.
Ideally, vaccination should be given before the start of immunosuppressive therapy
.
If immunosuppressive therapy has been started, the vaccine should be vaccinated at the time when the level of immunosuppression is lowest
.
Whether and when a booster vaccination is needed after the initiation of PCV13 remains to be determined
.
Under certain immunosuppressive treatments, immunogenicity may be reduced.
If possible, the immune response should be verified one month after vaccination, and children who are still immunosuppressed should be verified regularly
.

It is recommended that all children with autoimmune diseases vaccinated with pneumococcal vaccine should be vaccinated before the start of immunosuppressive therapy
.
If immunosuppressive therapy has been started, the vaccine should be vaccinated at the time when the level of immunosuppression is lowest
.

Meningococcal vaccine recommendations

Meningococcal vaccine recommendations

   Monovalent (capsular group A and C) or quadrivalent (MenACWY) meningococcal conjugate vaccines and vaccines against serogroup B (MenB) are recommended in several European countries and the United States and Canada, depending on various epidemics Meningococcal serogroups in different parts of the world
.
Patients with acquired complement deficiency, such as those receiving the monoclonal antibody eculizumab, and other children receiving immunosuppressive therapy, are also at risk of splenic dysfunction and should receive meningococcal immunization in time
.

Tetanus-diphtheria-pertussis polio vaccine recommendation

Tetanus-diphtheria-pertussis polio vaccine recommendation

   According to the unique national immunization guidelines, it is recommended that all children with immune-mediated diseases be vaccinated against tetanus, diphtheria, whooping cough and polio
.
The timing and number of doses depend on the number of previously received doses and the interval since the last vaccination
.
In young people, after the initial vaccination, a booster dose of diphtheria/tetanus vaccine should be given more than healthy people, that is, once every 10 years
.

The timing and number of doses depend on the number of previously received doses and the interval since the last vaccination
.
In young people, after the initial vaccination, a booster dose of diphtheria/tetanus vaccine should be given more than healthy people, that is, once every 10 years
.

Haemophilus influenzae type B (Hib) vaccine recommendation

Haemophilus influenzae type B (Hib) vaccine recommendation

   Inoculation of Hib vaccine should be carried out in accordance with national immunization guidelines
.
According to current epidemiology, Hib vaccine is not recommended after 5 years of age , even in immunosuppressed patients, except in the Czech Republic, Greece, the United States and Canada
.

Hib vaccine is not recommended after 5 years of age

Other vaccines: rabies, Japanese encephalitis, typhoid parenteral vaccine, tick-borne encephalitis

Other vaccines: rabies, Japanese encephalitis, typhoid parenteral vaccine, tick-borne encephalitis

   Before going to the affected area, vaccinations against rabies, Japanese encephalitis or typhoid fever should be made according to the national immunization guidelines for specific dangerous situations
.
Before planning international travel, these indications should be discussed separately with an expert
.

Vaccination against rabies, Japanese encephalitis or typhoid fever

Special cases

Special cases

Intravenous immunoglobulin for treatment of children

Intravenous immunoglobulin for treatment of children

   In the case of treatment with IVIg, if the vaccine is vaccinated 1-4 weeks (or longer) before or after IVIg, the immune response to the live attenuated vaccine may be reduced
.
Live vaccines should be given 2 weeks before IVIg or delayed 3-11 months after IVIg, depending on the dose
.
If IVIg is used for treatment within 14 days after live vaccination , the vaccine should be validated 3-11 months after IVIg treatment and re-vaccinated if necessary
.
  

If the vaccine is administered 1-4 weeks (or longer) before or after IVIg, the immune response to the live attenuated vaccine may be reduced
.
Live vaccines should be given 2 weeks before IVIg or delayed 3-11 months after IVIg, depending on the dose
.
Verify the vaccine 3-11 months after IVIg treatment

Treating children with B-cell depletion drugs

Treating children with B-cell depletion drugs

   Within 6-9 months after anti-CD20 monoclonal antibody or anti-BLyS treatment, the immune response is severely impaired because many plasma cells that produce antibodies have a short lifespan and require replacement of CD20+ precursor cells
.
In addition, the number of memory B cells in the bone marrow is also reduced.
The B cells that return from the bone marrow to the peripheral blood have an immature phenotype (CD27−IgD−) or naive (CD27−IgD+) instead of memory B cells
.
The development of new memory B cells seems to have been delayed for many years
.
However, permanent plasma cells may not be affected by B cell depletion drugs
.
Therefore, it is recommended to perform an immunotherapy before using the anti-CD20 depletion antibody
.
For inactivated vaccines, the secondary immunization can be performed 6 months after these treatments, but for live attenuated vaccines, it can only be performed after 12 months
.

It is recommended to perform an immunotherapy before using the anti-CD20 depletion antibody
.
For inactivated vaccines, the secondary immunization can be performed 6 months after these treatments, but for live attenuated vaccines, it can only be performed after 12 months
.

Immunosuppressive therapy during pregnancy

Immunosuppressive therapy during pregnancy

    When some immunosuppressive drugs pass through the placental barrier, immunosuppressive drugs for 6-8 months can be found in newborns, especially if the mother takes these drugs at the end of pregnancy
.
These drugs affect the development of the neonatal immune system and also affect the response to vaccines
.

    The European Union for Immunization recommends that if the use of biological agents is stopped before the 22nd week of pregnancy, the infant should be vaccinated at the normal time
.
However, if the mother continues to receive immunosuppressive therapy for more than 22 weeks, she should receive live-attenuated vaccines (including BCG, rotavirus, oral polio, MMR, and VZV) after 6 months
.
It can also measure the level of metabolism in the baby's blood
.
On the contrary, inactivated vaccines can be vaccinated at the normal time
.

If the use of biologics is stopped before the 22nd week of pregnancy, the baby should be vaccinated at the normal time
.
However, if the mother continues to receive immunosuppressive therapy for more than 22 weeks, she should receive live-attenuated vaccines (including BCG, rotavirus, oral polio, MMR, and VZV) after 6 months
.
Inactivated vaccines can be vaccinated at normal times
.

   Most csDMARD, bDMARD and tsDMARD are contraindications during breastfeeding, with the exception of antimalarials, sulfapyridine, AZT, cyclosporine, tacrolimus, colchicine, prednisone, Ig and anti-TNF because of their higher Less transfer to breast milk
.
Therefore, children who are exposed to immunosuppressive drugs only during breastfeeding can be vaccinated normally
.

Only children exposed to immunosuppressive drugs during breastfeeding can be vaccinated normally
.

Original source:

Blanchard-Rohner G, Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide.
Front Immunol 2021;12

Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide.
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