Document text
Principal Investigator: Michael A Barry
Organization: MAYO CLINIC ROCHESTER
Fiscal Year: 2024
Award: $745,752
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Most gene-based vaccines are replication-defective mRNA, DNA, or adenovirus (Ad) vaccines. In each case,
the vaccine delivers its one copy of an antigen gene and expresses "1X" of the antigens that are encoded by the
vaccine. We developed single cycle Ad (SC-Ad) vaccines that replicate vaccine antigen genes up to 10,000-fold
in every cell to amplify antigen production but do not produce infectious progeny viruses. When RD-Ad and SC-
Ad6 expressing HIV-1 antigens or SARS-CoV-2 spike are compared, SC-Ad produces 100 times more antigen
than RD-Ad and generates significantly higher antibodies than RD-Ad-Spike or mRNA vaccines. When spike-
immunized animals were challenged 10.5 months after single immunization, SC-Ad reduced SARS-CoV-2 lung
viral loads and damage and preserved body weights better than RD-Ad.
During the COVID-19 pandemic, we tested SC-Ads expressing SIV gag and clade C HIV-1 Env in rhesus
macaques by intramuscular (IM), intranasal (IN), and intravaginal (IVAG) routes of immunization in combination
with IM co-immunization with adjuvanted clade C SOSIP protein. When the macaques were challenged vaginally
with clade C SHIV.CH505.375H.dCT 1.5 years after last vaccine, PBS, IN, and IM vaccinated animals became
infected with similar kinetics with only one IN animal resisting infection. In contrast, 50% of the IVAG macaques
resisted vaginal challenge.
These data suggest there are great merits to creating a mucosal barrier against incoming SHIV at the site of viral
entry. Given this, this project will determine the reproducibility of this protection and examine how vaginal
immunization drives local-regional immune responses in the female reproductive tract (FRT) and if these
responses might be amplified by co-immunization in this site.
Proof of concept here for being able to “push” immune responses into the FRT in macaques will allow these
approaches to be translated for humans, to protect not just women, but all sexes and gender identities from
vaginal, rectal, or penile exposures to HIV-1.
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2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Simian Immunodeficiency Viruses><Site><Surface><Testing><Time><Transgenes><Translating><Vaccinated><Vaccination><Vaccine Antigen><Vaccines><Vagina><Vaginal Administration><Viral><Viral Burden><Viral Load><Viral Load result><Viral load measurement><Virion><Virus><Virus Particle><Virus-HIV><Woman><Work><Wuhan coronavirus><benchmark><booster dose><booster shot><booster vaccine><colorectum><combat><coronavirus disease 2019 S protein><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 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respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex identity><sexual identity><simian HIV><simian human immunodeficiency virus><spike proteins on SARS-CoV-2><transgene><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine boost><vaccine candidates against SARS-CoV-2><vaccine delivery><vaccine for novel coronavirus><vaccines preventing COVID><vaccines to prevent COVID><virus load><women's genital tract><women's reproductive tract>