Initial Exploratory Study on the Feasibility of Rectal Vaccine Delivery

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Initial Exploratory Study on the Feasibility of Rectal Vaccine Delivery (2 replies)

Posted by: aroma vadi

Date: 11/25/2025 2:03:10 AM Reply

 

 

 

Discoverer and Author: Dr. Majid Mollanadali Pishnamaz, PhD in Applied Chemistry, Promoted to the Rank of Professor

 

 

 

 

 

Initial Assessment of Immunogenicity of Inactivated (Influenza) and Live-Attenuated (BCG) Vaccines in Human Volunteers Using Suppositories: An Exploratory Proof-of-Concept Study for Systemic Vaccine Delivery via the Rectal Route

 

 

 

 

 

Abstract

 

 

 

 

 

Background: Injectable vaccine delivery faces widespread limitations, including the demand for Cold Chain infrastructure, the management of biohazardous waste, and patient acceptance challenges (such as Vaccinophobia). This research introduces a novel, non-invasive delivery method with significant potential to revolutionize vaccinations: the anorectal absorption pathway via suppositories.

 

 

Methods: Suppositories were prepared with active antigen doses equivalent to clinical injectable doses: 0.5 mL for the Influenza vaccine (inactivated) and 0.1 mL for the BCG vaccine (live-attenuated). An exploratory proof-of-concept study was conducted on three (3) human volunteers. Immunogenicity was evaluated by measuring Specific Antibody Titers in the volunteers' serum as initial evidence.

 

 

Results: The results demonstrated the production of a primary and detectable Humoral Response of specific antibodies against the antigens of both vaccines in the bloodstream of all three volunteers. These data strongly suggest the possibility of systemic antigen absorption via the anorectal suppository.

 

 

Discussion and Conclusion: These findings reinforce the potential for bypassing First-Pass Hepatic Metabolism through this delivery method. This approach offers potential operational benefits such as eliminating injection barriers, facilitating self-administration, and observing enhanced thermal stability (up to 35∘C) for inactivated vaccines. However, the limited scope of this initial study means that conducting larger studies and controlled clinical trials in the future is absolutely necessary to definitively confirm the Bioavailability and clinical efficacy.

 

 

 

 

 

1. Introduction

 

 

 

 

 

The rectal (anorectal) route is recognized as a highly absorptive mucosal tissue. A key advantage of this pathway is its vascular network, which (especially from the lower sections of the rectum) shunts blood directly to the Inferior Vena Cava, and appears to bypass the hepatic portal venous system.

 

 

...This potential Bypass of First-Pass Effect is a major pharmacokinetic advantage for bio-molecules sensitive to enzymatic degradation (such as proteins), as it prevents Metabolic Degradation in the liver.

 

 

The primary goal of this study is to provide preliminary evidence (Proof-of-Concept) for the exploratory hypothesis that vaccine antigens, in the form of prepared suppositories, have the capability for effective systemic absorption and the ability to generate an Immune Response (Immunogenicity) in human volunteers.

 

 

 

 

 

2. Materials and Methods

 

 

 

 

 

2.3. Immunogenicity Proof-of-Concept Study

 

 

 

 

 

A strictly exploratory and uncontrolled study was performed on three (3) human volunteers. This study was designed solely to investigate the feasibility of this delivery concept. Volunteers were placed under a vaccination protocol with suppositories containing the Influenza and BCG vaccines.

 

 

Immunogenicity (the vaccine's ability to stimulate an immune response) was measured by assaying the titers of Anti-Antigen Specific Antibodies in the volunteers' serum samples, using validated immunological assays (such as ELISA or Hemagglutination Inhibition Assay) as a primary indicator of the humoral response.

 

 

 

 

 

3. Results

 

 

 

 

 

The results of the immunogenicity assay demonstrated a positive and initial humoral response:

 

 

 

 

 

Influenza Vaccine: Detectable and positive titers of specific antibodies against the influenza virus were observed in the serum of all three volunteers.

 

 

 

 

 

BCG Vaccine: Similarly, the production of specific antibodies against the BCG vaccine antigens was also observed in the circulation of all three volunteers.

 

 

 

 

 

These results offer strong evidence that the active antigen, at injectable equivalent doses, can penetrate the systemic circulation via the rectal route and retain its immunogenicity. However, due to the severely limited sample size (n=3) and the exploratory nature of this study, these findings should be considered only as an initial proof-of-concept, and definitive clinical or final pharmacokinetic results cannot be extracted from them.  

 

 

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4. Discussion

 

 

 

 

 

4.1. Pharmacokinetic and Immunogenicity Implications

 

 

 

 

 

The creation of a positive antibody response in the initial sample indicates the potential for maintaining acceptable Bioavailability of the antigen through the rectal route. This technical success is likely due to the effective avoidance of the hepatic portal system, which allows the vaccine protein molecules to reach the Mucosa-Associated Lymphoid Tissue (MALT) in the rectum and subsequently the systemic circulation without initial destruction. This achievement is a significant exploratory step in the field of large biomolecule delivery.

 

 

 

 

 

4.3. Potential for Development and Public Health Impact

 

 

 

 

 

This exploratory study holds the potential to establish a universal delivery platform for vaccines. ... However, to transition this potential into a real public health strategy, more comprehensive immunological studies and efficacy trials with larger sample sizes are the necessary next steps to definitively confirm the clinical efficacy of this delivery method.

 

 

 

 

 

5. Conclusion

 

 

 

 

 

The discovery and observation of an initial immunogenicity response to vaccines (Influenza and BCG) via anorectal suppositories is a promising advance in vaccinology. In addition to facilitating vaccination operations, this non-invasive and apparently effective delivery method provides the crucial advantage of increased thermal stability up to 35∘C for inactivated vaccine variants.

 

 

The results of this preliminary and limited study (n=3) only demonstrate the Feasibility (or Proof-of-Concept) of this method. For definitive validation, full clinical efficacy assessment, optimal dose determination, and expansion of this platform to other vaccines, future extensive, controlled, and scheduled research is absolutely necessary to comprehensively confirm the bioavailability and safety of this delivery method and enable its transition into a global strategy.