The safety and efficacy of non-typeable Haemophilus influenzae and Moraxella catarrhalis vaccine in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials

Tiankui Shuai ¹ Jing Liu ² Meijun Dong ³ Peng Wu ⁴ Lu Zhang ¹ Zhouzhou Feng ¹ Wenqiang Li ¹ Jian Liu ^1*

• ¹ First Hospital of Lanzhou University, Lanzhou, Gansu Province, China
• ² the Second Affiliated Hospital of Xi' an Medical University, Xian, China., Xian, China
• ³ 省人民医院, Lanzhou, China
• ⁴ KeyMed Biosciences Inc.,, Chengdu, Sichuan,, China

Background: Non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are major pathogens implicated in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). Their involvement contributes to antibiotic resistance and poses significant immune challenges, underscoring the need for targeted vaccine strategies. This systematic review and meta-analysis assessed the safety and efficacy of NTHi-Mcat/NTHi vaccines in COPD patients.Research design and methods: Randomized controlled trials (RCTs) assessing the safety and efficacy of NTHi-Mcat/NTHi vaccines for COPD were systematically searched across four databases (PubMed, CENTRAL, Embase, and Medline) from inception to October 2024. Meta-analyses were conducted using random-effects or fixed-effects models, with subgroup analyses to investigate possible sources of heterogeneity.Results: This analysis included eight RCTs involving 1,574 participants, primarily conducted in Europe (n=3) and Australia (n=2), with interventions administered orally or intramuscularly at varying frequencies (twice or three times).The Meta-analyses revealed that the NTHi-Mcat/NTHi vaccine did not affect the incidence of acute exacerbations of COPD (relative risk (RR): 1.02, 95% confidence interval (CI): 0.76 to 1.36), all-cause mortality (RR: 0.91, 95% CI: 0.38 to 2.21), and hospitalization rate (RR: 0.50, 95% CI: 0.09 to 2.77). Regarding safety, the NTHi-Mcat/NTHi vaccine did not significantly increase the risk of serious adverse events (RR: 1.00, 95% CI: 0.84 to 1.19) or grade 3 serious events (RR: 1.20, 95% CI: 0.93 to 1.53). However, it was associated with a higher risk of local and systemic reactions, including pain (RR: 5.33, 95% CI: 1.98 to 14.33), swelling (RR: 12.15, 95% CI: 4.67 to 31.67), redness (first dose: RR: 12.74, 95% CI: 3.48 to 46.59; second dose: RR: 11.55, 95% CI: 3.90 to 34.22), headaches (RR: 1.20, 95% CI: 1.00 to 1.43), erythema (RR: 15.38, 95% CI: 5.64 to 41.92), and fever (after the second dose: RR: 2.33, 95% CI: 1.24 to 4.38).Conclusions: Although the NTHi-Mcat/NTHi vaccines were well-tolerated in COPD patients, they did not significantly reduce the risk of exacerbations or mortality. These findings suggest that further research is needed to validate these results and identify potential subgroups that may derive clinical benefit.