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Adjuvant effect of the human metapneumovirus (HMPV) matrix protein in HMPV subunit vaccines
Laetitia Aerts1, Chantal Rhéaume1, Julie Carbonneau1
1Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec and Université Laval, Quebec City, Quebec G1V 4G2, Canada.
Abstract:
The human metapneumovirus (HMPV) fusion (F) protein is the most immunodominant protein, yet subunit vaccines containing only this protein do not confer complete protection. The HMPV matrix (M) protein induces the maturation of antigen-presenting cells in vitro. The inclusion of the M protein into an F protein subunit vaccine might therefore provide an adjuvant effect. We administered the F protein twice intramuscularly, adjuvanted with alum, the M protein or both, to BALB/c mice at 3 week intervals. Three weeks after the boost, mice were infected with HMPV and monitored for 14 days. At day 5 post-challenge, pulmonary viral titres, histopathology and cytokine levels were analysed. Mice immunized with F+alum and F+M+alum generated significantly more neutralizing antibodies than mice immunized with F only [titres of 47 ± 7 (P<0.01) and 147 ± 13 (P<0.001) versus 17 ± 2]. Unlike F only [1.6 ± 0.5 × 10(3) TCID50 (g lung)(-1)], pulmonary viral titres in mice immunized with F+M and F+M+alum were undetectable. Mice immunized with F+M presented the most important reduction in pulmonary inflammation and the lowest T-helper Th2/Th1 cytokine ratio. In conclusion, addition of the HMPV-M protein to an F protein-based vaccine modulated both humoral and cellular immune responses to subsequent infection, thereby increasing the protection conferred by the vaccine.
Insights
Adding the human metapneumovirus (HMPV) matrix (M) protein to fusion (F) protein vaccines enhances immune responses and protection against HMPV infection. This M protein inclusion boosts neutralizing antibodies and reduces viral load and inflammation.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- The human metapneumovirus (HMPV) fusion (F) protein is immunodominant but insufficient alone for complete vaccine protection.
- The HMPV matrix (M) protein promotes antigen-presenting cell maturation in vitro, suggesting adjuvant potential.
Purpose of the Study:
- To investigate if including the HMPV M protein in an F protein subunit vaccine enhances protective immunity against HMPV infection.
- To evaluate the impact of M protein co-administration on humoral and cellular immune responses.
Main Methods:
- BALB/c mice were immunized twice with F protein, adjuvanted with alum, M protein, or both.
- Mice were challenged with HMPV, and pulmonary viral titers, histopathology, and cytokine levels were assessed on day 5 post-challenge.
Main Results:
- F+M+alum and F+alum vaccines significantly increased neutralizing antibodies compared to F only.
- Pulmonary viral titers were undetectable in mice immunized with F+M or F+M+alum, unlike the F only group.
- Mice receiving F+M showed reduced pulmonary inflammation and a lower Th2/Th1 cytokine ratio.
Conclusions:
- Co-administration of HMPV M protein with F protein in a subunit vaccine enhances protective immunity.
- The M protein acts as an effective adjuvant, modulating both humoral and cellular immune responses to HMPV.
- This strategy improves vaccine efficacy beyond F protein alone, offering better protection against HMPV challenge.
