On 2017 Sep 29, Elena Gavrilova commented:

The detailed answers on all E.V. Dueva’s comments regarding this article have been already published on the PLOS One page. Anyway, I am, as an author, glad that the article attracts the attention of the readers – it is in line with authors purpose to draw readers for a broad discussion of a new subject we have been working on. Here below the short answers on some comments are represented. The article provides all the details and data and it has been written as openly and clearly as possible. The nature of the posted comments confirms that the article is fully transparent for the readers so they have an opportunity to familiarize themselves with these results and arrive at their own opinion. The principal E.V. Dueva’s statement is incorrect since the product described in the article is not homeopathic. The technology used in some steps of the released-active forms of antibodies production is similar to the one used in the preparation of homeopathic products. This is obvious and indicated in papers and patents about these products. At the same time it should be highlighted that homeopathy therapy principle is the similarity principle, which is the basis for special approaches for the homeopathic drug investigation and application in practice. Quite the reverse, products containing released-active forms of antibodies have all the necessary attributes of standard pharmacological medicine. In addition, I would like to emphasize that the article is dedicated not to the investigation of basic features of released-active products, but the possibility to expand the use of ELISA as a method of activity assessment of RA forms of antibodies to interferon-gamma (RA forms of Abs to IFNg). The fact that RA forms of Abs to IFNg are the Active Pharmaceutical Ingredient of commercially available drug product ‘Anaferon for children’ was not in any way concealed from the readers as it is clearly stated in the article (section ‘Materials and Methods’, subsection ‘Preparation of anti-IFN-gamma release-active dilutions’). The article clearly states the purpose of the study, namely to assess the ELISA approach as the assay for the detection of RA forms of Abs to IFNg. Design of the study and conducted work have fully addressed its purpose.

On 2017 Sep 15, Evgenia V Dueva commented:

This is an article about homeopathy, although the word «homeopathy» is never explicitly mentioned. The authors state: «RA forms of Abs to IFN-gamma contain release-active dilutions of antibodies to IFN-gamma consisting of a mixture of C12+C30+C50 final dilutions».

Here the object of the study is described using homeopathic terminology. When translated this means the following: a mixture of rabbit polyclonal antibodies to recombinant human interferon gamma diluted to the power of 10^-24, 10^-60 and 10^-100. Or in other words: containing no measurable quantities of antibodies. Even the 10^-24 dilution is indistinguishable from zero. Note that these preparations were eventually diluted even further (at least to ~10^-28) during the actual experiments. The claim that dilutions of substances beyond Avogadro’s limit have specific effects is a homeopathic claim.

The authors, including Oleg Epstein – CEO of OOO "NPF "MATERIA MEDICA HOLDING" – a Russian Company that markets a number of drugs which contain active ingredients diluted beyond Avogadro’s limit, are not telling the truth when they state that «There are no patents, products in development or marketed products to declare».

In fact, «RA forms of Abs to IFN-gamma» are the claimed «active ingredient» of one of the Company’s products called «Anaferon for Children». The article by Gavrilova et al. is listed on the Company’s website in the section called «Anaferon for Children», subheading «Articles, Preclinical» http://materiamedica.ru/en/stat/articles/. It is also actively self-cited by the Company in contexts such as «Data obtained using ELISA and piezoelectric immunosensors evidences that anaferon is able to modify IFNγ affinity to specific antibodies to IFNγ» https://medi.ru/info/11531/ and even in statements that the main mechanism of action for «Anaferon» is to improve ligand to receptor binding affinity.

We revealed critical flaws in the key assumptions and conclusions made by the authors. One can find our critical comment on this article at PLOS One page.

Considering that the actual data consists of just four ELISA runs, one cannot conclude that sufficient effort has been made to investigate such an extraordinary claim as the measurable biological effects of ultra-low homeopathic dilutions beyond Avogadro’s limit.

On 2017 Sep 15, Evgenia V Dueva commented:

This is an article about homeopathy, although the word «homeopathy» is never explicitly mentioned. The authors state: «RA forms of Abs to IFN-gamma contain release-active dilutions of antibodies to IFN-gamma consisting of a mixture of C12+C30+C50 final dilutions».

Here the object of the study is described using homeopathic terminology. When translated this means the following: a mixture of rabbit polyclonal antibodies to recombinant human interferon gamma diluted to the power of 10^-24, 10^-60 and 10^-100. Or in other words: containing no measurable quantities of antibodies. Even the 10^-24 dilution is indistinguishable from zero. Note that these preparations were eventually diluted even further (at least to ~10^-28) during the actual experiments. The claim that dilutions of substances beyond Avogadro’s limit have specific effects is a homeopathic claim.

The authors, including Oleg Epstein – CEO of OOO "NPF "MATERIA MEDICA HOLDING" – a Russian Company that markets a number of drugs which contain active ingredients diluted beyond Avogadro’s limit, are not telling the truth when they state that «There are no patents, products in development or marketed products to declare».

In fact, «RA forms of Abs to IFN-gamma» are the claimed «active ingredient» of one of the Company’s products called «Anaferon for Children». The article by Gavrilova et al. is listed on the Company’s website in the section called «Anaferon for Children», subheading «Articles, Preclinical» http://materiamedica.ru/en/stat/articles/. It is also actively self-cited by the Company in contexts such as «Data obtained using ELISA and piezoelectric immunosensors evidences that anaferon is able to modify IFNγ affinity to specific antibodies to IFNγ» https://medi.ru/info/11531/ and even in statements that the main mechanism of action for «Anaferon» is to improve ligand to receptor binding affinity.

We revealed critical flaws in the key assumptions and conclusions made by the authors. One can find our critical comment on this article at PLOS One page.

Considering that the actual data consists of just four ELISA runs, one cannot conclude that sufficient effort has been made to investigate such an extraordinary claim as the measurable biological effects of ultra-low homeopathic dilutions beyond Avogadro’s limit.

On 2017 Sep 29, Elena Gavrilova commented:

The detailed answers on all E.V. Dueva’s comments regarding this article have been already published on the PLOS One page. Anyway, I am, as an author, glad that the article attracts the attention of the readers – it is in line with authors purpose to draw readers for a broad discussion of a new subject we have been working on. Here below the short answers on some comments are represented. The article provides all the details and data and it has been written as openly and clearly as possible. The nature of the posted comments confirms that the article is fully transparent for the readers so they have an opportunity to familiarize themselves with these results and arrive at their own opinion. The principal E.V. Dueva’s statement is incorrect since the product described in the article is not homeopathic. The technology used in some steps of the released-active forms of antibodies production is similar to the one used in the preparation of homeopathic products. This is obvious and indicated in papers and patents about these products. At the same time it should be highlighted that homeopathy therapy principle is the similarity principle, which is the basis for special approaches for the homeopathic drug investigation and application in practice. Quite the reverse, products containing released-active forms of antibodies have all the necessary attributes of standard pharmacological medicine. In addition, I would like to emphasize that the article is dedicated not to the investigation of basic features of released-active products, but the possibility to expand the use of ELISA as a method of activity assessment of RA forms of antibodies to interferon-gamma (RA forms of Abs to IFNg). The fact that RA forms of Abs to IFNg are the Active Pharmaceutical Ingredient of commercially available drug product ‘Anaferon for children’ was not in any way concealed from the readers as it is clearly stated in the article (section ‘Materials and Methods’, subsection ‘Preparation of anti-IFN-gamma release-active dilutions’). The article clearly states the purpose of the study, namely to assess the ELISA approach as the assay for the detection of RA forms of Abs to IFNg. Design of the study and conducted work have fully addressed its purpose.