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Updated: Sep 21, 2026
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Construction and evaluation of a pertactin-deficient live attenuated pertussis vaccine candidate BPZE1 derivative
Luis Solans1, Anne-Sophie Debrie1, Loïc Coutte1
1Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
Insights
A new pertussis nasal vaccine, BPZE1P, was developed to overcome limitations of existing vaccines. This pertactin-deficient strain effectively colonizes the respiratory tract and protects against Bordetella pertussis infection, even with pre-existing immunity.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Pertussis, caused by Bordetella pertussis, remains a significant respiratory threat, particularly to infants.
- Current vaccines reduce incidence but fail to prevent infection or transmission.
- Pre-existing antibodies to pertactin can hinder the efficacy of live attenuated nasal vaccines like BPZE1.
Purpose of the Study:
- To develop a modified live attenuated nasal vaccine, BPZE1P, lacking pertactin.
- To evaluate BPZE1P's colonization, immunogenicity, and protective efficacy in preclinical models.
- To assess BPZE1P's performance in the presence of pre-existing antibodies against pertactin.
Main Methods:
- Construction of a pertactin-deficient BPZE1 derivative (BPZE1P).
- Assessment of respiratory tract colonization and antibody induction in mice.
- Evaluation of protection against Bordetella pertussis challenge in vaccinated mice.
- Comparison of BPZE1P and BPZE1 efficacy in mice with pre-existing antibodies.
Main Results:
- BPZE1P demonstrated efficient colonization and induced comparable antibody levels to BPZE1 in mice.
- BPZE1P showed enhanced colonization compared to BPZE1 in the presence of pre-existing antibodies.
- Both BPZE1 and BPZE1P provided robust protection against Bordetella pertussis challenge, including pertactin-deficient strains.
- BPZE1P exhibited superior efficacy against pertactin-deficient strains compared to acellular pertussis vaccines.
Conclusions:
- BPZE1P is a promising pertactin-deficient live attenuated nasal vaccine candidate.
- BPZE1P overcomes vaccine take limitations caused by pre-existing anti-pertactin antibodies.
- This novel vaccine offers potential for improved pertussis prevention, especially against diverse Bordetella pertussis strains.
Abstract:
Pertussis, mainly caused by Bordetella pertussis, is a severe respiratory disease that can be fatal, especially in young infants. Vaccines, massively implemented since the middle of the last century, have substantially reduced the pertussis incidence, but have not been able to fully control the disease. One of the shortcomings of current pertussis vaccines is their inability to prevent infection by and transmission of B. pertussis, in contrast to immunity following natural infection. We have developed the live attenuated nasal vaccine BPZE1 and have shown that it prevents both disease and B. pertussis infection in preclinical models. This vaccine is now in clinical development. However, the initial clinical studies have suggested that vaccine take is hampered by pre-existing antibodies to pertactin. Here, we have constructed a pertactin-deficient BPZE1 derivative called BPZE1P in order to overcome this limitation. BPZE1P colonized the murine respiratory tract as efficiently as BPZE1 and induced antibodies at levels similar to those elicited by BPZE1. In the presence of pre-existing antibodies induced by acellular pertussis vaccination, BPZE1P colonized the mouse respiratory tract more efficiently than BPZE1. Both vaccines protected equally well the murine lungs and noses from challenge with laboratory and clinical strains of B. pertussis, including pertactin-deficient strains, against which current acellular pertussis vaccines are less efficient. BPZE1P may thus be an interesting alternative to BPZE1 to overcome vaccine take limitations due to pre-existing antibodies to pertactin.
