Intranasal vaccination induces robust systemic immunity against HIV and SARS-CoV-2 in animal models

Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abn1413″ width=”558″ height=”478″/>

Antigen-specific IgG and IgA plasma cells are produced in mice after intranasal immunization with ampha-protein without induction of anti-PEG antibodies. BALB/c mice (n = 3 animals per group) were immunized with 5 μg of amph-eOD mixed with 25 μg of cdGMP adjuvant and boosted with the same formulation 6 weeks later. Female reproductive tract (FRT) and bone marrow (BM) eOD-specific IgG and IgA antibody-secreting cells (ASCs) were assessed by ELISPOT at 20 weeks post-immunization. (A) Representative well images and (B) quantification of antibody-secreting plasma cells per 500,000 cells are shown. All data are presented as mean ± sem (C) of serum samples from mice immunized as in Fig. 4A and F with saponin (collected at week 11) or cdGMP adjuvants (collected at week 12) were compared with a standard anti-PEG IgG reference for anti-PEG IgG by ELISA. Credit: Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abn1413

Although most viruses directly infect mucosal cells, the majority of vaccines are routinely administered because of suboptimal immune cell-mediated incompatibility.

SARS-CoV-2 is transmitted through the mucous membrane of the nose, HIV through the mucous membrane of the genitals and anus. But these two are not the only ones, many other viruses, including those that cause influenza, measles, and polio, and many others, can infect humans through mucous membranes.

Now, a large multi-institutional team of scientists is working on an intranasal method of immunization to determine whether it is possible to produce effective protection against HIV and SARS-CoV-2 by directly inoculating mucosal cells. Scientists have achieved these feats by developing a method to deliver vaccine proteins across the sometimes inflexible mucosal barrier. To date, research has been conducted in animal models—mice and nonhuman primates—but the results already suggest a promising approach for testing in human clinical trials.

“Immunization strategies to combat the HIV epidemic and emerging threats such as SARS-CoV-2 require protection from mucosal portals of pathogens,” wrote Brittany Hartwell of the Massachusetts Institute of Technology and colleagues from several US institutions. Their investigation was published Science Translational Medicine.

“Direct vaccination through air surfaces is effective for driving mucosal immunity, but poor vaccine uptake through mucosa and epithelial lining is limited. The major blood protein albumin is constitutively bidirectionally transcytosed through the air epithelium.”

Albumin is often resistant to vaccines that penetrate mucosal cells. As a result of this barrier, the absorption of the vaccine through the mucosal tract is limited. By developing a new strategy to efficiently deliver a payload to mucosal cells, a team of researchers is on the verge of a breakthrough in the science of delivering immunizing proteins.

In their journal report, Hartwell and colleagues describe what they call an amph-protein strategy that allows immune-stimulating proteins to “hitchhike” across mucosal surfaces. Their ampha-proteins consist of viral proteins conjugated to an amphiphilic tail that binds albumin, a blood protein, and thus allows it to cross the mucosa by interacting with the neonatal Fc receptor. The neonatal Fc receptor or FcRn is also known as the Brambell receptor. It protects antibodies, IgG or immunoglobulin-G, and albumin from catabolism, and transports IgG across epithelial cells.

The team turned to animal models to see if this experimental intranasal approach could effectively deliver immunizing proteins across mucosal surfaces and generate strong vaccine immunity against two known viruses: HIV and SARS-CoV-2. The study showed that intranasal vaccination induced systemic immunity.

In experiments, scientists found that intranasal vaccines can induce stronger and more protective antibody responses than injectable vaccines. But they were also aware that some experimental mucosal vaccines were limited by poor uptake of the vaccine across the mucosa.

What they want to know is whether it is possible to change how the vaccine is delivered, and in turn, show that the mucosal route of inoculation leads to a stronger antibody response. If they can do that, and their research eventually proves it, then they would be on the way to a vaccine and some potential option that could provide protection against HIV and SARS-CoV-2. Their first step was to develop a vaccine platform that could be tested in mice and non-human primates.

When combined with the receptor-binding domain of the HIV protein Env gp120 or SARS-CoV-2, the ampha-proteins elicited strong anti-virus antibody responses in the serum and nasal mucosa of immunized mice and non-human primates.

“Intranasal immunization with alpha-conjugated HIV Env gp120 or SARS-CoV-2 receptor-binding domain proteins induces 100-1000-fold higher antigen-specific IgG and IgA titers in serum, upper and lower respiratory tract mucosa, and distal mucosal genitourinary mice compared to the unaltered protein,” Hartwell wrote, referring to immunoglobulin-G and immunoglobulin-A antibodies.

“Immunization of the ampha receptor binding domain induced high titers of SARS-CoV-2-neutralizing antibodies in serum, nasal lavage, and bronchoalveolar lavage. In addition, intranasal immunization of ampha protein in rhesus macaques elicited a 10-fold higher antigen- and IG-specific response. With serum compared to intact protein in the nasal mucosa, supporting the translational potential of this approach,” Hartwell asserted in the paper.

The results suggest that using amph-protein vaccines to deliver antigen across the mucosal epithelium is a promising strategy for promoting mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases, as additional vaccines using this strategy have been developed. “Ampha-proteins were retained in the nasal mucosa of mice and nonhuman primates and showed greater tissue uptake … leading to enhanced germinal center responses in nasal-associated lymphoid tissues,” Hartwell concluded.

Francis Soka, a professor in the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco, praised Hartwell and colleagues’ vaccine research for its innovative approach. “These findings may improve the vaccine’s ability to prevent HIV infection and contribute to the goal of a SARS-CoV-2 variant-agnostic vaccine,” Soka said in a related Focus article (published in Science Translational Medicine) examines the clinical implications of the study.


A new method of nasal vaccine delivery could lead to better vaccines against HIV and COVID-19


More information:
Brittany L. Hartwell et al, Intranasal vaccination with lipid-conjugated immunogens promotes transmucosal uptake of antigen to promote mucosal and systemic immunity, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abn1413

Francis C. Szoka, The Hitchhiker’s Guide to Mucosal and Systemic Immunity, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.adc8697

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Quote: Intranasal vaccination induces potent systemic immunity against HIV and SARS-CoV-2 in animal models (2022, August 17) August 18, 2022 https://medicalxpress.com/news/2022-08-intranasal-vaccination-potent- Immunity is taken from -hiv.html

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