Assessment of replicon ribonucleic acid COVID-19 vaccine in nonhuman primates

In a recent article posted to the bioRxiv* preprint server, researchers explored the immunogenicity of a replicon ribonucleic acid (repRNA) coronavirus disease 2019 (COVID-19) vaccine, repRNA-CoV2S, in pigtail macaques.

Study: A replicon RNA vaccine induces durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. Image Credit: nobeastsofierce/Shutterstock


The global COVID-19 pandemic resulted in the rapid establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Despite the availability of multiple approved vaccinations, the SARS-CoV-2 pandemic is still ongoing, with resurgent cases in numerous countries.

The continuous development of SARS-CoV-2 vaccines has been prompted by the emergence of SARS-CoV-2 variants of concern (VOC), decreasing immunity among the vaccinated, indications that vaccinations may not prevent the virus transmission, and unequal vaccine distribution. Additionally, the public health concern about the diminishing immunity in the vaccinated individuals has led to the recommendation of booster doses to maintain the cross-protective immunity established by the presently authorized COVID-19 vaccines against emerging VOCs.

An ideal COVID-19 vaccine should prevent upper airway infection, thereby lowering transmission potential, offer protection from severe respiratory illness, and induce long-lasting immunity against SARS-CoV-2 without requiring repeated booster immunizations to solve the current public health catastrophe caused by COVID-19.

About the study

In the present report, the scientists used a pigtail macaque model of COVID-19 to assess a novel self-amplifying repRNA SARS-CoV-2 vaccine encoding the spike (S) protein, i.e., repRNA-CoV2S. They looked at how well the repRNA-CoV2S vaccination protected these nonhuman primates immunized with 5, 25, and 50 μg doses both during the height of neutralizing antibody responses and after they had declined.

The team examined the influences of dose and interval across priming and booster vaccinations on the immunogenicity of the COVID-19 repRNA-CoV2S vaccine. They assessed whether repRNA-CoV2S offers protection against viral replication across the respiratory mucosa even when neutralizing antibody reactions had diminished to undetectable titers.

Further, the authors explored if the repRNA-CoV2S vaccination confers long-lasting protection from clinical illness and lung pathology caused by SARS-CoV-2 infection. Trained research staff thoroughly examined the animals for indications of COVID-19, such as decreased appetite, respiratory distress, general appearance, and lethargy. On day 7 post-infection, formalin-fixed lung tissue was evaluated for lung pathology under blind conditions.

The researchers analyzed the effect of vaccination on cytokine reaction across the lungs following the SARS-CoV-2 challenge. On days 3, 5, and 7 following infection, they measured chemokines and cytokines in the bronchial alveolar lavages (BAL) and blindly assessed their correlation with clinical disease severity. In addition, the investigators determined whether the vaccine lessened BAL inflammatory responses.

Furthermore, the team investigated if the vaccinated pigtail macaques had a robust and quick anamnestic recall antibody response after the SARS-CoV-2 challenge.


The authors found that the current self-amplifying repRNA-CoV2S vaccine elicited potent neutralizing and binding antibody reactions in pigtail macaques in response to the SARS-CoV-2 challenge. They observed that binding antibody reactions were preserved, whereas neutralizing antibodies declined to unmeasurable titers six months following the vaccination. 

Nevertheless, neutralizing antibody reactions were recalled immediately and imparted protection against illness when the nonhuman primates were viral challenged seven months post-vaccination. This inference was derived from the evident decrease in virus replication and pathology across the lower respiratory tract, declined viral shedding across the nasal cavity, and decreased pro-inflammatory cytokine levels in the lungs.

Interestingly, the study results indicated that lower BAL SARS-CoV-2 burden significantly correlated with higher concentrations of binding antibodies and not serum neutralizing antibodies. The research reveals the effectiveness of the COVID-19 vaccination with no measurable amounts of neutralizing antibodies present at the time of challenge.

The study data showed that a self-amplifying repRNA vaccination could confer long-lasting protection against SARS-CoV-2 infection in pigtail macaques. Moreover, these data suggest that this vaccine can lower viral shedding even following the waning of the neutralizing antibody responses to undetectable titers.


The study findings depicted that neutralizing antibody reactions triggered by the repRNA-CoV2S vaccination contracted to very low or unmeasurable levels by almost seven months post-immunization in nonhuman primates. However, preserved binding antibodies and a prompt anamnestic recall response mediated protection against infection and lung illness during the SARS-CoV2 challenge seven months post-vaccination.  

The current study implies that COVID-19 protection may involve non-neutralizing binding antibodies or other forms of adaptive immunity. Besides, it offers concrete proof that the SARS-CoV-2 vaccine's protective immunological B cell memory endures and can continue to afford protection even when neutralizing antibodies have declined to undetectable levels. The study findings indicate that the repRNACoV2S vaccine may prevent the spread of SARS-CoV-2 and protect from severe COVID-19.

Cumulatively, the present data favors continuing pre-clinical and clinical research on the repRNACoV2S vaccine.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Megan A. O'Connor, David W. Hawman, Kimberly Meade-White, et al. (2022). A replicon RNA vaccine induces durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned. bioRxivdoi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antibodies, Antibody, B Cell, Cell, Chemokines, Coronavirus, Coronavirus Disease COVID-19, covid-19, Cytokine, Cytokines, immunity, Immunization, Lethargy, Lungs, Pandemic, Pathology, Protein, Public Health, Research, Respiratory, Respiratory Illness, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine, Virus

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Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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