Promising Interim Results for Sinopharm’s Inactivated Whole Virion SARS-CoV-2 Vaccine

The COVID-19 pandemic has led to intense scientific efforts to achieve an effective vaccine for global distribution. Many different approaches to vaccine design are underway. A recent study published in the journal The Lancet Infectious Diseases in October 2020 reports on a potentially successful inactivated virus vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The ongoing COVID-19 pandemic is the only outbreak to date in which the time from the identification of a pathogen to the presentation of the results of the first clinical trial for a specific vaccine against the pathogen was less than nine months. By September 2020, more than 39 vaccine candidates have begun testing, with more than 200 more in preclinical development.

Preliminary data from these vaccine trials is vital to understanding how safe and effective vaccines can be, as they are designed to counteract a new virus and many adverse effects can be found only by observation and not prediction.

Complete virus vaccine

Chinese researchers have published a study of a whole virion SARS-CoV-2 vaccine candidate with inactivated and recently tested aluminum hydroxide adjuvant beta-Propiolactone. The trial was a ½ phase, double blind, randomized controlled trial in healthy adults. Including people over the age of 60, this was a pioneering trial in offering evidence of the effects of the vaccine in older people for the first time among all SARS-CoV-2 inactivated trials.

The vaccine was administered in the classic initial boost format, at three different concentrations, in phase 1, using an escalation protocol. The doses used were 2 μg, 4 μg and 8 μg,

Immunogenicity and safety in the elderly

The researchers found high tolerability in both the 18-59-year-old and 60-year-old age groups. Adverse event rates were lower in the latter group, with 47% of 72 younger participants reporting adverse events within 28 days of vaccination, compared with ~ 20% of an equal number of 60-year-olds or more.

Immunogenicity was comparable in both groups, as measured by geometric mean titers during a 50% virus neutralization assay at 14 days after the booster dose.

The researchers also looked for cross-reactivity, finding that neutralizing antibodies could continue to be effective despite some degree of drift, promising to cover divergent strains if they emerged in the community.

Optimal Prime-Boost Delay

In phase 2, the first part of the trial looked at the effects of using a booster protocol with only 14 or 21 days between the two doses, instead of 28 days. The researchers observed that in a 21-day interval from the first to the booster, the 4 μg dose of the vaccine elicited the highest immune response. When the interval was shortened, immunogenicity was markedly lower.

Implications and future directions

The results confirm an earlier study from Wuhan that used the same type of inactivated virus particle to neutralize antibody titers and adverse events. This indicates that the efficacy of the vaccine is preserved even when manufactured by different manufacturers. The efficacy of the whole virus particle may be due to the presence of all epitopes.

However, the study also shows that it is possible to stabilize the structure of the main antigens. The use of appropriate inactivation methods is crucial to prevent the induction of non-neutralizing and possibly harmful antibodies by altered epitopes. The current study showed no evidence of disease-enhancing effects in various animal models, secondary to vaccine-induced antibodies, after exposure to the virus.

The study is not conclusive, as more detailed and long-term follow-up is necessary in a wider range of animal models to explore such antibody-dependent enhancement phenomena. A second area to investigate is whether the vaccine elicits specific and long-lasting CD4 + T cell responses, as they are necessary for optimal antibody generation, as well as for the activation of cytotoxic CD8 + T cells, necessary for viral elimination in case of incomplete neutralization by antibodies.

The vaccine is currently undergoing phase 3 testing to verify its safety and efficacy and the duration of protection. This is expected to contribute to the body of knowledge on the protective effects of inactivated vaccines against SARS-CoV-2.

Source

Isakova-Sivak, I. A promising vaccine against inactivated whole virion SARS-Cov-2. The lancet Infectious diseases. DOI: https: //doi.org/10.1016/S1473-3099 (20) 30832-X. https://www.thelancet.com/journals/lanpsy/article/PIIS1473-3099(20)30832-X/fulltext