Intranasal vaccination against angiotensin II type 1 receptor and pneumococcal surface protein A attenuates hypertension and pneumococcal infection in rodents

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Abstract

Objectives:

To combat global increases in the prevalence of lifestyle-related diseases and concomitant infectious diseases, we aimed to develop an innovative intranasal vaccine that simultaneously targets both hypertension and pneumonia, is not given by invasive injection, and offers prolonged therapeutic effect and reduced frequency of administration.

Methods:

Angiotensin II type 1 receptor-pneumococcal surface protein A (AT1R–PspA) vaccine, consisting of a cationic nanometer-sized hydrogel incorporating AT1R partial peptide conjugated with PspA and cyclic diguanylate monophosphate adjuvant, was created and given intranasally to spontaneously hypertensive rats (SHRs). Antigen-specific antibodies and blood pressure were examined to evaluate immune responses and the antihypertensive effect of the vaccine. To examine the protective effect of antibodies induced by vaccination on pneumococcal infection, sera obtained from immunized SHRs were incubated with a lethal dose of Streptococcus pneumoniae and then administered to mice.

Results:

Five doses of AT1R–PspA nasal-vaccine-induced AT1R-specific serum IgG antibody production and attenuated the development of hypertension in SHRs in the long term. Both in-vitro and in-vivo studies revealed that responses to angiotensin II were suppressed in vaccinated rats. Mice passively immunized with sera obtained from AT1R–PspA-vaccinated SHRs were protected from lethal pneumococcal infection.

Conclusion:

Intranasal immunization with AT1R–PspA vaccine has the potential to simultaneously attenuate the development of hypertension and protect from lethal pneumococcal infection.

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