Making sense of fall vaccine guidance for the immunocompromised

This year, professional medical organizations are stepping up to provide recommendations going into cold and flu season. The Infectious Disease Society of America’s (IDSA) guidelines for people who are immunocompromised are the most relevant for people with primary immunodeficiency (PI), but other organizations have published guidelines as well:

• Children and adolescents (American Academy of Pediatrics; AAP).
• Immunocompetent and older adults (American Academy of Family Physicians; AAFP).
• Pregnant people (American College of Obstetricians and Gynecologists; ACOG).

COVID-19, influenza (the flu), and respiratory syncytial virus (RSV) can all be serious, life-threatening illnesses in people with PI. Getting vaccinated and making sure everyone in your household is vaccinated is one of the best ways to protect yourself from these germs. Your healthcare provider may also recommend monoclonal antibodies, depending on your situation.

Because SARS-CoV-2 and influenza strains shift from year to year, it’s important to get seasonal COVID and flu shots every year. While immunoglobulin (Ig) replacement therapy protects against many diseases, it takes months to manufacture and generally does not have enough antibodies against the latest virus strains to protect you well. That’s why the foundation’s Medical Advisory Committee (MAC) continues to recommend that everyone with PI, whether you’re on Ig or not, get these seasonal vaccines.

Respiratory syncytial virus (RSV) is different. Only people who have not been vaccinated against RSV before need to get immunized.

COVID-19

COVID-19 has now settled into a pattern of two peaks a year: one starting in August and another in January. Updated 2026-2027 COVID-19 vaccines are arriving just as the late summer peak hits. They target one strain of the SARS-CoV-2 virus, the XFG subvariant.

Here’s what to know:

1. People 6 months through 64 years old who are immunocompromised should receive one dose of an updated COVID-19 vaccine approved for their age.
   1. If an immunocompromised person has not been vaccinated against COVID before, use the 2024-2025 guidance from the Centers for Disease Control and Prevention (CDC).
   2. While there is no specific recommendation for more than one dose, IDSA stated “A second booster dose can be given ≥2-6 months after dose one based on shared decision making and current levels of transmission.”
2. Children ages 6-23 months old who are not immunocompromised should receive at least one dose of an updated COVID-19 vaccine approved for their age. If they have not been vaccinated or did not complete a previous series, they may need two doses at least eight weeks apart.
3. Adults ages 19-64 years old who are not immunocompromised should receive one dose of an updated COVID-19 vaccine approved for their age.
4. All adults 65+ years of age should receive two doses of an updated COVID-19 vaccine approved for their age six months apart.
5. All pregnant people should receive one dose of an updated COVID-19 vaccine approved for their age as early as possible during pregnancy.
6. A separate IDSA guideline recommends that people 12+ years old who are moderately to severely immunocompromised receive the monoclonal antibody pemivibart to prevent COVID infections. Pemivibart is meant to add a layer of protection, and can be given every three months.

There are four Food and Drug Administration (FDA)-approved COVID vaccines available, as well as one FDA-authorized monoclonal antibody. None of the vaccines are live, so they are all safe for people with PI and their loved ones.

Influenza

For 2026-2027, flu vaccines protect against two influenza A and one influenza B strains. Importantly, all three strains are new this year.

Here’s what to know:

1. All people ≥6 months old should receive at least one dose of an updated flu vaccine approved for their age. Children who have not previously been vaccinated for flu may need two doses at least four weeks apart.
2. People who are immunocompromised and their household members should not receive FluMist, the live, attenuated nasal spray vaccine. While IDSA did not recommend a particular vaccine, they stated, “High-dose or adjuvanted influenza vaccines provide more robust immune response, which may be of particular importance in immunocompromised patients.” 
3. Pregnant people should receive an inactivated or recombinant flu vaccine.
4. People who are 65+ years of age should try to get either the adjuvanted, high-dose, mRNA, or recombinant vaccines if possible.

There are nine Food and Drug Administration (FDA)-approved flu vaccines available. Only FluMist is a live vaccine.

Respiratory syncytial virus

Unlike COVID and the flu, you don’t need to get vaccinated for RSV more than once in your lifetime. However, IDSA recently expanded its recommendations on who should get vaccinated.

Here’s what to know:

1. People ≥18 years old who are immunocompromised should receive one RSV vaccine dose if they have not previously been vaccinated.
2. Note that IDSA recommends shared clinical decision making for RSV vaccination in children under 18 who are immunocompromised. Currently, RSV vaccines have not been approved by the FDA for use in children.
3. People who are 75+ years of age should receive one RSV vaccine dose if they have not previously been vaccinated.
4. From September through February, people pregnant for the first time should receive one dose of Abrysvo at 32-36 weeks of pregnancy if they have not already been vaccinated for RSV.
5. Babies up to 8 months old should receive one dose of an RSV monoclonal antibody during their first RSV season if their mother was not vaccinated during pregnancy.
6. Babies 8-19 months old who are at high risk, including those with PI, should receive a second dose of nirsevimab going into their second RSV season.

Three RSV vaccines and two monoclonal antibodies are currently approved. None of the vaccines contain live virus, so they are all safe for people with PI and their loved ones.

Vaccine timing and other tips

IDSA’s guidelines specifically address timing of vaccines for PI and other categories of immunocompromise. Since the COVID, flu, and RSV vaccines recommended for people with PI are not live vaccines, there is no need to time vaccination around intravenous (IVIG) or subcutaneous (SCIG) Ig infusions. However, there are other situations where timing is important, including:

• B cell targeted biologics, such as rituximab: ≥ 2 weeks prior to treatment or ≥ 3-6 months after last infusion.
• Other immune-suppressing biologics, such as adalimumab: ≥ 2 weeks prior to treatment or ≥ 3 months after last infusion.
• Hematopoietic stem cell transplant (HSCT) or CAR-T therapy: ≥ 3 months after HSCT or CAR-T, ≥ 3-6 months after B cell targeted CAR-T.

The guidelines point out that it is safe to get all the fall vaccines you need at the same time. However, each vaccine should be given at a site that is at least one inch away from any other site. Being able to get all your vaccines during one appointment simplifies planning, especially if you’re timing vaccines around other medical considerations.

Also, remember that vaccines are a crucial tool during respiratory virus season, but you should take advantage of other tools, too. Masking in public places, avoiding sick people, and good hand and surface hygiene can cut down on your exposure to all germs, not just the big ‘cold and flu season’ threats.

Finally, make sure you’re prepared in case you do get COVID, the flu, or RSV. How will you get tested? What antivirals does your healthcare provider recommend that you take (or avoid) and how will you get them? What symptoms should you pay the most attention to?