B cells oppose Mycoplasma pneumoniae vaccine enhanced disease and limit bacterial colonization of the lungs

Tyler D Gavitt; Arlind B Mara; Meagan L Goodridge; Rosemary Grace Ozyck; Emily Reinhardt; Jeremy M Miller; Morgan Hunte; Edan R Tulman; Salvatore Frasca Jr; Lawrence K Silbart; Steven J Geary; Steven M Szczepanek

doi:10.1038/s41541-022-00556-z

B cells oppose Mycoplasma pneumoniae vaccine enhanced disease and limit bacterial colonization of the lungs

NPJ Vaccines. 2022 Oct 31;7(1):130. doi: 10.1038/s41541-022-00556-z.

Authors

Tyler D Gavitt^{1

2

3}, Arlind B Mara^{1

2

3}, Meagan L Goodridge^{1

2}, Rosemary Grace Ozyck^{1

2}, Emily Reinhardt^{1

4}, Jeremy M Miller^{1

2

3}, Morgan Hunte^{1

2

5}, Edan R Tulman^{1

2

3}, Salvatore Frasca Jr¹, Lawrence K Silbart^{2

6}, Steven J Geary^{7

8

9}, Steven M Szczepanek^{10

11

12}

Affiliations

¹ Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, 06238, USA.
² Center of Excellence for Vaccine Research, University of Connecticut, Storrs, CT, 06238, USA.
³ US Animal Vaccinology Research Coordination Network, Storrs, CT, 06238, USA.
⁴ Connecticut Veterinary Medical Diagnostic Laboratory, Storrs, CT, 06238, USA.
⁵ Sanofi, Meriden, CT, 06450, USA.
⁶ Department of Allied of Health Sciences, University of Connecticut, Storrs, CT, 06238, USA.
⁷ Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, 06238, USA. steven.geary@uconn.edu.
⁸ Center of Excellence for Vaccine Research, University of Connecticut, Storrs, CT, 06238, USA. steven.geary@uconn.edu.
⁹ US Animal Vaccinology Research Coordination Network, Storrs, CT, 06238, USA. steven.geary@uconn.edu.
¹⁰ Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, 06238, USA. steven.szczepanek@uconn.edu.
¹¹ Center of Excellence for Vaccine Research, University of Connecticut, Storrs, CT, 06238, USA. steven.szczepanek@uconn.edu.
¹² US Animal Vaccinology Research Coordination Network, Storrs, CT, 06238, USA. steven.szczepanek@uconn.edu.

Abstract

Development of an effective vaccine for Mycoplasma pneumoniae has been hindered by reports of Vaccine Enhanced Disease (VED) in test subjects vaccinated and challenged in studies conducted in the 1960s. The exact mechanism of disease exacerbation has yet to be fully described, but host immune responses to Lipid-Associated Membrane Proteins (LAMPs) lipoprotein lipid moieties have been implicated. LAMPs-induced exacerbation appears to involve helper T cell recall responses, due in part to their influence on neutrophil recruitment and subsequent inflammatory responses in the lung. Herein, we characterized the functions of host B cell responses to M. pneumoniae LAMPs and delipidated-LAMPs (dLAMPs) by conducting passive transfer and B cell depletion studies to assess their contribution to disease exacerbation or protection using a BALB/c mouse model. We found that antibody responses to M. pneumoniae LAMPs and dLAMPs differ in magnitude, but not in isotype or subclass. Passive transfer, dLAMP denaturation, and monoclonal antibody studies indicate that antibodies do not cause VED, but do appear to contribute to control of bacterial loads in the lungs. Depletion of B cells prior to LAMPs-vaccination results in significantly enhanced pathology in comparison to B cell competent controls, suggesting a possible regulatory role of B cells distinct from antibody secretion. Taken together, our findings suggest that B cell antibody responses to M. pneumoniae contribute to, but are insufficient for protection against challenge on their own, and that other functional properties of B cells are necessary to limit exacerbation of disease in LAMPs-vaccinated mice after infection.

Grants and funding

NA/University of Connecticut (UCONN)