Infectious diseases play a central role in exacerbations of chronic respiratory diseases and are also responsible for the progression of the disease.
of the underlying disease. For many important pathogens
of the respiratory tract, effective vaccines are now available. Improved pneumococcal vaccines and vaccination against the RS virus are the latest developments in this field.
More severe pneumococcal infections occurred after the COVID pandemic than before. Many children are carriers of Streptococcus pneumoniae and then infect adults, so both groups need to be vaccinated equally. Pneumococci cause many infections such as otitis media, community-acquired pneumonia, sepsis and meningitis. “For us as respiratory physicians, the topic is extremely important, as we have more problems with asthma and COPD exacerbations in the case of pneumonia, for example,” recalled PD Dr. Jessica Rademacher, Center for Internal Medicine, Clinic for Pneumology, Hannover Medical School (D) [1], who gave an overview of the most important vaccinations.
Streptococcus pneumoniae
Streptococcus pneumoniae is a gram-positive, extracellular, opportunistic pathogen that colonizes the mucosal surfaces of the human upper respiratory tract. 27% to 65% of children and <10% of adults are carriers of pneumococci.
There are two types of pneumococcal vaccines available: The polysaccharide-based vaccine (PPV23) has been around for many years, but a major problem with this vaccine is the limited B-cell stimulation and antibody production, plus the lack of memory B-cell training leads to a waning immune response over a period of one to two years.
The pneumococcal conjugate vaccines (PCVs) contain pneumococcal polysaccharide antigens that are covalently linked to immunogenic carrier proteins. They induce a T cell-dependent humoral immune response and stimulate T cells to support B cells in the production of antibodies and thus create a better immune memory.
For many years, the approved PCVs for adults have included PCV13, which is also administered to children and adults in combination or as a follow-up vaccination with PPSV23. At the end of 2021 and beginning of 2022, further 15- and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20) were developed and approved for the prevention of invasive diseases and pneumonia caused by S. pneumoniae in adults. The advantage of these new vaccines is that they contain more serotypes: 22F and 33F in PCV15 and 22F, 33F, 8, 10A, 11A, 12F and 15B in PCV20 (Fig. 1).
Serotype 3 is currently a challenge, explained Dr. Rademacher. This is responsible for a large proportion of infections, especially serious infections. The problem is that antibody formation is not as good with PCV20 as with PCV15. However, it is not yet known whether this difference is clinically relevant. There are therefore recommendations, particularly for immunocompromised patients, to carry out sequential vaccination with PCV15 followed by PPSV23 in immunosuppressed patients. The current recommendation of the Advisory Committee on Immunization Practices (ACIP) is to either give PCV20 alone or a sequential vaccination with PCV15 and PPSV23.
Influenza
Influenza is also a major burden, particularly for patients with chronic obstructive pulmonary disease (COPD), asthma and chronic respiratory diseases. Every flu infection leads to exacerbations in these patients.
There are also newer formulations of the influenza vaccine. “They are not perfect in their effectiveness, but we can improve the vaccination with the MF 59 adjuvant,” says Dr. Rademacher confidently. MF 59 is an oil-in-water emulsion and has been shown to reduce outbreak and hospitalization rates in vulnerable patients. In addition, vaccination with high-dose haemagglutinin (60 μg) has been shown to reduce infection, pneumonia and hospitalization rates, especially in older patients. A study has shown that the combination of influenza and pneumococcal vaccination in people with chronic obstructive pulmonary disease achieves the best results in this patient group with regard to the exacerbation rate [3]. 474 COPD patients were included and vaccinated with the trivalent seasonal influenza vaccine (TIV, n=109), the 23-valent pneumococcal polysaccharide vaccine (PPSV23, n=69) or both (n=296).
The overall effectiveness in preventing AECOPD, pneumonia and associated hospitalizations was
- 70%, 59% and 58% in the TIV group
- 54%, 53% and 46% in the PPSV23 group
- 72%, 73% and 69% in the TIV&PPSV23 group
Efficacy of the vaccine was
- 84%, 77% and 88% in the TIV group
- 63%, 74% and 66% in the PPSV23 group
- 82%, 83% and 91% in the TIV&PPSV23 group
Looking ahead, the expert expressed the hope that there could one day be better influenza vaccines. “There are currently two clinical trials with mRNA vaccine techniques in phase 3, with phase I trials promising better prophylactic efficacy.” A nucleoside-modified messenger RNA lipid nanoparticle vaccine encoding haemagglutinin antigens of all 20 known subtypes of influenza A and B viruses could also become an option.
Respiratory syncytial virus
In 2023, two vaccines against respiratory syncytial virus (RSV) for adults aged ≥60 years received EU approval. Both are protein-based vaccines, but RSVPreF3 is adjuvanted, whereas RSVPreF is not. In a study [4], the adjuvanted protein-based vaccine showed convincing efficacy in the prevention of lower respiratory tract infections and severe respiratory tract infections in adults aged ≥60 years, regardless of RSV subtype and the presence of concomitant diseases (Fig. 2).
The study is designed for an observation period of three years. “So we will receive the data from the second year this autumn, but we already know that the vaccination does not need to be repeated every year,” explained Dr. Rademacher. “It remains stable after the second year, so it may not need to be refreshed every year.”
In 2023, the US Advisory Committee on Immunization Practices (ACIP) recommended that adults aged ≥60 years can receive a single dose of the RSV vaccine. Corresponding recommendations are also needed from other countries, according to the expert. According to ACIP recommendation 2023, all patients with one of the following underlying diseases or other factors associated with an increased risk of severe RSV disease should be vaccinated.
Chronic underlying diseases that are associated with an increased risk:
- Lung diseases (such as COPD and asthma)
- Cardiovascular diseases (e.g. congestive heart failure and coronary heart disease)
- Diabetes mellitus
- Neurological or neuromuscular diseases
- Kidney diseases
- Liver disease
- Hematologic diseases
Other underlying diseases which, according to the doctor’s assessment, may increase the risk of severe respiratory disease.
- Other factors associated with an increased risk:
- Frailty
- Old age
- Stay in a nursing home or other long-term care facility
- Other underlying factors that the healthcare provider believes may increase the risk of severe respiratory disease.
Take-Home Messages
- Vaccinations are important and are underused.
- The new pneumococcal vaccine has more serotypes and sequential vaccination, including PPSV23, is being pushed into the background.
- As things stand today, flu vaccination techniques could be better in terms of their effectiveness.
- Data on RSV vaccines from Phase 3 trials were published in 2023.
- The first RSV vaccine types are showing good efficacy, and the first ACIP recommendations for older adults and underlying medical conditions are online.
Sources:
- Session “Respiratory infections”; Lecture: “Update on vaccination to preventable respiratory infections”; ERS Congress 2023, Milan, 11.09.2023.
- Simon S, Joean O, Welte T, Rademacher J.: The role of vaccination in COPD: influenza, SARS-CoV-2, pneumococcus, pertussis, RSV and varicella zoster virus. European Respiratory Review 2023; 32: 230034; doi: 10.1183/16000617.0034-2023.
- Li Y, et al: Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations. Respirology 2022; 27: 844-853; doi: 10.1111/resp.14309.
- Papi A, et al: Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med 2023; 388: 595-608; doi: 10.1056/NEJMoa2209604.
InFo PNEUMOLOGIE & ALLERGOLOGIE 2023; 5(4): 28-29 (published on 6.11.23, ahead of print)
