NIH grant: Novel In-Clinic Molecular Adjuvant Enhances Antiviral Humoral Immunity of Vaccines Across Sexes (1R21AI202433-01)

retained text

NIH grant 1R21AI202433-01: Novel In-Clinic Molecular Adjuvant Enhances Antiviral Humoral Immunity of Vaccines Across Sexes
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: ZHAOYANG  YOU. Award: $234370.
Start: 2026-08-07T00:00:00.
Novel In-Clinic Molecular Adjuvant Enhances Antiviral Humoral Immunity of Vaccines Across Sexes
Abstract
Females typically generate more effective humoral immunity of vaccines (e.g., influenza vaccine) than males.
Discovering safe and effective adjuvants, which are crucial for vaccinations, to enhance immunogenicity of
viral antigens across sexes is an urgent need. We have found the in-clinic small molecule latanoprost that
promotes intradermally co-delivered influenza H1N1 Hemagglutinin (HA) or SARS-CoV-2 Spike (S) protein
vaccine for inducing HA-specific IgG1 or S-specific neutralizing antibody (NAb) across sexes in C57BL/6 mice.
HA or S protein vaccine alone induces a remarkable difference of IgG1 or NAb responses in females vs. males;
interestingly, latanoprost preferentially promotes IgG1 or NAb responses to HA or S protein vaccine in males,
resulting in a reduced difference to a comparable level of IgG1 or NAb in males vs. females. Conventional type
1 DC (cDC1) are tied to long-lasting NAb responses following latanoprost-adjuvanted vaccinations. There are
more migratory cDC1 in the skin of females than males; intriguingly, latanoprost increases skin migratory cDC1
across sexes, with a greater effectiveness in males, leading to a similar level of migratory cDC1 in the skin of
females vs. males. Combined data from both females and males demonstrate that latanoprost-adjuvanted
vaccines are superior to non-adjuvanted vaccines in eliciting humoral responses to viral antigens. We
hypothesize that latanoprost increases migratory cDC1 and eliminates their differences between
females and males in the skin to enhance antiviral humoral immunity of vaccines across sexes. We will
1) explore the mechanisms by which latanoprost enhances humoral responses to viral antigens in males and
females, and 2) develop latanoprost-adjuvanted vaccines across sexes. If successful, we will discover
latanoprost as a novel in-clinic molecular adjuvant to enhance humoral responses to viral antigens in males
and females and develop clinically translatable latanoprost-adjuvanted influenza and SARS-CoV-2 vaccines
across sexes which differ from past reports for female-biased humoral responses to conventional vaccines.

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